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122-412: Genes are the common factor of the qualities of most human-inherited traits. Study of human genetics can answer questions about human nature, can help understand diseases and the development of effective treatment and help us to understand the genetics of human life. This article describes only basic features of human genetics; for the genetics of disorders please see: medical genetics . For information on

244-439: A differential diagnosis and recommend appropriate testing. These tests might evaluate for chromosomal disorders, inborn errors of metabolism , or single gene disorders. Chromosome studies are used in the general genetics clinic to determine a cause for developmental delay or intellectual disability, birth defects, dysmorphic features, or autism. Chromosome analysis is also performed in the prenatal setting to determine whether

366-469: A medical specialty with particular attention to hereditary disorders . Branches of clinical genetics include: Examples of genetic syndromes that are commonly seen in the genetics clinic include chromosomal rearrangements (e.g. Down syndrome , 22q11.2 deletion syndrome , Turner syndrome , Williams syndrome ), Fragile X syndrome , Marfan syndrome , neurofibromatosis , Huntington disease , familial adenomatous polyposis , and many more. In Europe ,

488-455: A population bottleneck caused by purposeful ( assortative ) breeding or natural environmental factors, the deleterious inherited traits are culled. Island species are often very inbred, as their isolation from the larger group on a mainland allows natural selection to work on their population. This type of isolation may result in the formation of race or even speciation , as the inbreeding first removes many deleterious genes, and permits

610-450: A species may not be able to adapt to changes in environmental conditions. Each individual will have similar immune systems, as immune systems are genetically based. When a species becomes endangered , the population may fall below a minimum whereby the forced interbreeding between the remaining animals will result in extinction . Natural breedings include inbreeding by necessity, and most animals only migrate when necessary. In many cases,

732-486: A "snapshot" of an individual's health status. The unique status of genetic information and inherited disease has a number of ramifications with regard to ethical, legal, and societal concerns. On 19 March 2015, scientists urged a worldwide ban on clinical use of methods, particularly the use of CRISPR and zinc finger , to edit the human genome in a way that can be inherited. In April 2015 and April 2016, Chinese researchers reported results of basic research to edit

854-436: A consistent and uniform animal model for experimental purposes and enables genetic studies in congenic and knock-out animals. In order to achieve a mouse strain that is considered inbred, a minimum of 20 sequential generations of sibling matings must occur. With each successive generation of breeding, homozygosity in the entire genome increases, eliminating heterozygous loci. With 20 generations of sibling matings, homozygosity

976-606: A diagram showing the ancestral relationships and transmission of genetic traits over several generations in a family. Square symbols are almost always used to represent males, whilst circles are used for females. Pedigrees are used to help detect many different genetic diseases. A pedigree can also be used to help determine the chances for a parent to produce an offspring with a specific trait. Four different traits can be identified by pedigree chart analysis: autosomal dominant, autosomal recessive, x-linked, or y-linked. Partial penetrance can be shown and calculated from pedigrees. Penetrance

1098-546: A fetus is affected with aneuploidy or other chromosome rearrangements. Finally, chromosome abnormalities are often detected in cancer samples. A large number of different methods have been developed for chromosome analysis: Biochemical studies are performed to screen for imbalances of metabolites in the bodily fluid, usually the blood (plasma/serum) or urine, but also in cerebrospinal fluid (CSF). Specific tests of enzyme function (either in leukocytes, skin fibroblasts, liver, or muscle) are also employed under certain circumstances. In

1220-467: A form of distant linebreeding occurs. Again it is up to the assortative breeder to know what sort of traits, both positive and negative, exist within the diversity of one breeding. This diversity of genetic expression, within even close relatives, increases the variability and diversity of viable stock. Systematic inbreeding and maintenance of inbred strains of laboratory mice and rats is of great importance for biomedical research. The inbreeding guarantees

1342-456: A gene, trait, or disorder is transferred through the Y chromosome. Since Y chromosomes can only be found in males, Y linked traits are only passed on from father to son. The testis determining factor , which is located on the Y chromosome, determines the maleness of individuals. Besides the maleness inherited in the Y-chromosome there are no other found Y-linked characteristics. A pedigree is

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1464-404: A particular recessive genetic mutation . Except in certain rare circumstances, such as new mutations or uniparental disomy , both parents of an individual with such a disorder will be carriers of the gene. These carriers do not display any signs of the mutation and may be unaware that they carry the mutated gene. Since relatives share a higher proportion of their genes than do unrelated people, it

1586-409: A patient is given an infusion of the missing enzyme "Z" or cofactor therapy to increase the efficacy of any residual "Z" activity. Dietary restriction and supplementation are key measures taken in several well-known metabolic disorders, including galactosemia , phenylketonuria (PKU), maple syrup urine disease , organic acidurias and urea cycle disorders . Such restrictive diets can be difficult for

1708-470: A population through purifying selection . Inbreeding is a technique used in selective breeding . For example, in livestock breeding , breeders may use inbreeding when trying to establish a new and desirable trait in the stock and for producing distinct families within a breed, but will need to watch for undesirable characteristics in offspring, which can then be eliminated through further selective breeding or culling . Inbreeding also helps to ascertain

1830-519: A population to become fixed for certain traits, like having too many bones in an area, like the vertebral column of wolves on Isle Royale or having cranial abnormalities, such as in Northern elephant seals , where their cranial bone length in the lower mandibular tooth row has changed. Having a high homozygosity rate is problematic for a population because it will unmask recessive deleterious alleles generated by mutations, reduce heterozygote advantage, and it

1952-520: A recessive trait or disease to be displayed two copies of the trait or disorder needs to be presented. The trait or gene will be located on a non-sex chromosome. Because it takes two copies of a trait to display a trait, many people can unknowingly be carriers of a disease. From an evolutionary perspective, a recessive disease or trait can remain hidden for several generations before displaying the phenotype. Examples of autosomal recessive disorders are albinism , cystic fibrosis . X-linked genes are found on

2074-462: A severe winter weather related population crash. These studies show that inbreeding depression and ecological factors have an influence on survival. The Florida panther population was reduced to about 30 animals, so inbreeding became a problem. Several females were imported from Texas and now the population is better off genetically. A measure of inbreeding of an individual A is the probability F (A) that both alleles in one locus are derived from

2196-566: A significantly higher chance of reaching repeated results with future offspring. Additionally, consanguineous parents possess a high risk of premature birth and producing underweight and undersized infants. Viable inbred offspring are also likely to be inflicted with physical deformities and genetically inherited diseases. Studies have confirmed an increase in several genetic disorders due to inbreeding such as blindness, hearing loss, neonatal diabetes, limb malformations, disorders of sex development , schizophrenia and several others. Moreover, there

2318-441: A single copy—inherited from either parent—is enough to cause this trait to appear. This often means that one of the parents must also have the same trait, unless it has arisen due to an unlikely new mutation. Examples of autosomal dominant traits and disorders are Huntington's disease and achondroplasia . Autosomal recessive traits is one pattern of inheritance for a trait, disease, or disorder to be passed on through families. For

2440-494: A small colony was discovered in the Point Sur region in the 1930s. Since then, the population has grown and spread along the central Californian coast to around 2,000 individuals, a level that has remained stable for over a decade. Population growth is limited by the fact that all Californian sea otters are descended from the isolated colony, resulting in inbreeding. Cheetahs are another example of inbreeding. Thousands of years ago,

2562-478: A small population for a period of time can lead to inbreeding within that population, resulting in increased genetic relatedness between breeding individuals. Inbreeding depression can also occur in a large population if individuals tend to mate with their relatives, instead of mating randomly. Due to higher prenatal and postnatal mortality rates, some individuals in the first generation of inbreeding will not live on to reproduce. Over time, with isolation, such as

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2684-478: A unique mechanism of dosage compensation . In particular, by way of the process called X-chromosome inactivation (XCI), female mammals transcriptionally silence one of their two Xs in a complex and highly coordinated manner. Genetic Chromosomal Medical genetics Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders . Medical genetics differs from human genetics in that human genetics

2806-509: A woman would produce twice the amount of normal X chromosome proteins. The mechanism for X inactivation will occur during the embryonic stage. For people with disorders like trisomy X , where the genotype has three X chromosomes, X-inactivation will inactivate all X chromosomes until there is only one X chromosome active. Males with Klinefelter syndrome , who have an extra X chromosome, will also undergo X inactivation to have only one completely active X chromosome. Y-linked inheritance occurs when

2928-406: Is Coffin–Lowry syndrome , which is caused by a mutation in ribosomal protein gene. This mutation results in skeletal, craniofacial abnormalities, mental retardation, and short stature. X chromosomes in females undergo a process known as X inactivation . X inactivation is when one of the two X chromosomes in females is almost completely inactivated. It is important that this process occurs otherwise

3050-434: Is a field of scientific research that may or may not apply to medicine, while medical genetics refers to the application of genetics to medical care. For example, research on the causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counselling people with genetic disorders would be considered part of medical genetics. In contrast,

3172-488: Is also denoted as the kinship coefficient between A and B. A particular case is the self-coancestry of individual A with itself, f(A,A), which is the probability that taking one random allele from A and then, independently and with replacement, another random allele also from A, both are identical by descent. Since they can be identical by descent by sampling the same allele or by sampling both alleles that happen to be identical by descent, we have f(A,A) = 1/2 + F(A)/2. Both

3294-567: Is an increased risk for congenital heart disease depending on the inbreeding coefficient (See coefficient of inbreeding ) of the offspring, with significant risk accompanied by an F =.125 or higher. The general negative outlook and eschewal of inbreeding that is prevalent in the Western world today has roots from over 2000 years ago. Specifically, written documents such as the Bible illustrate that there have been laws and social customs that have called for

3416-488: Is attempting to explain the genetic basis behind the child's developmental concerns in a compassionate and articulated manner that allows the potentially distressed or frustrated parents to easily understand the information. As well, genetic counselors normally take a family pedigree, which summarizes the medical history of the patient's family. This then aids the clinical geneticist in the differential diagnosis process and help determine which further steps should be taken to help

3538-473: Is detrimental to the survival of small, endangered animal populations. When deleterious recessive alleles are unmasked due to the increased homozygosity generated by inbreeding, this can cause inbreeding depression. There may also be other deleterious effects besides those caused by recessive diseases. Thus, similar immune systems may be more vulnerable to infectious diseases (see Major histocompatibility complex and sexual selection ). Inbreeding history of

3660-608: Is discussed in the following quotation on cattle: Meanwhile, milk production per cow per lactation increased from 17,444 lbs to 25,013 lbs from 1978 to 1998 for the Holstein breed. Mean breeding values for milk of Holstein cows increased by 4,829 lbs during this period. High producing cows are increasingly difficult to breed and are subject to higher health costs than cows of lower genetic merit for production (Cassell, 2001). Intensive selection for higher yield has increased relationships among animals within breed and increased

3782-548: Is evaluated through a structured program that begins with observation and progresses to independent practice under supervision, culminating in the ability to manage complex cases independently. Final certification involves a comprehensive assessment, which may include national examinations or the European Certificate in Medical Genetics and Genomics (ECMGG) . This certificate serves as a benchmark for high standards in

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3904-443: Is expected to increase the number of spontaneous abortions of zygotes, perinatal deaths, and postnatal offspring with birth defects. The advantages of inbreeding may be the result of a tendency to preserve the structures of alleles interacting at different loci that have been adapted together by a common selective history. Malformations or harmful traits can stay within a population due to a high homozygosity rate, and this will cause

4026-427: Is in contrast to the inheritance of traits on autosomal chromosomes, where both sexes have the same probability of inheritance. Since humans have many more genes on the X than the Y , there are many more X-linked traits than Y-linked traits. However, females carry two or more copies of the X chromosome, resulting in a potentially toxic dose of X-linked genes . To correct this imbalance, mammalian females have evolved

4148-816: Is in controlling for confounding between population substructure , environmental exposures, and health outcomes. Association studies can produce spurious results if cases and controls have differing allele frequencies for genes that are not related to the disease being studied, although the magnitude of this problem in genetic association studies is subject to debate. Various methods have been developed to detect and account for population substructure, but these methods can be difficult to apply in practice. Population substructure also can be used to advantage in genetic association studies. For example, populations that represent recent mixtures of geographically separated ancestral groups can exhibit longer-range linkage disequilibrium between susceptibility alleles and genetic markers than

4270-485: Is increasingly involved with individuals who have undertaken elective genetic and genomic testing . In some ways, many of the individual fields within medical genetics are hybrids between clinical care and research. This is due in part to recent advances in science and technology (for example, see the Human Genome Project ) that have enabled an unprecedented understanding of genetic disorders . Clinical genetics

4392-469: Is more likely that related parents will both be carriers of the same recessive allele, and therefore their children are at a higher risk of inheriting an autosomal recessive genetic disorder. The extent to which the risk increases depends on the degree of genetic relationship between the parents; the risk is greater when the parents are close relatives and lower for relationships between more distant relatives, such as second cousins, though still greater than for

4514-404: Is not as effective. Fixation of alleles most likely occurs through Muller's ratchet , when an asexual population's genome accumulates deleterious mutations that are irreversible. Despite all its disadvantages, inbreeding can also have a variety of advantages, such as ensuring a child produced from the mating contains, and will pass on, a higher percentage of its mother/father's genetics, reducing

4636-409: Is occurring at roughly 98.7% of all loci in the genome, allowing for these offspring to serve as animal models for genetic studies. The use of inbred strains is also important for genetic studies in animal models, for example to distinguish genetic from environmental effects. The mice that are inbred typically show considerably lower survival rates. Inbreeding increases homozygosity, which can increase

4758-930: Is overseen by the Royal Australasian College of Physicians with the Australasian Association of Clinical Geneticists contributing to authorship of the curriculum via their parent organization, the Human Genetics Society of Australasia . Metabolic (or biochemical) genetics involves the diagnosis and management of inborn errors of metabolism in which patients have enzymatic deficiencies that perturb biochemical pathways involved in metabolism of carbohydrates , amino acids , and lipids . Examples of metabolic disorders include galactosemia , glycogen storage disease , lysosomal storage disorders , metabolic acidosis , peroxisomal disorders , phenylketonuria , and urea cycle disorders . Cytogenetics

4880-551: Is primarily assortative breeding (see selective breeding ). Without the sorting of individuals by trait, a breed could not be established, nor could poor genetic material be removed. Homozygosity is the case where similar or identical alleles combine to express a trait that is not otherwise expressed (recessiveness). Inbreeding exposes recessive alleles through increasing homozygosity. Breeders must avoid breeding from individuals that demonstrate either homozygosity or heterozygosity for disease causing alleles. The goal of preventing

5002-458: Is the case for other populations. Genetic studies can use this admixture linkage disequilibrium to search for disease alleles with fewer markers than would be needed otherwise. Association studies also can take advantage of the contrasting experiences of racial or ethnic groups, including migrant groups, to search for interactions between particular alleles and environmental factors that might influence health. Inbreeding Inbreeding

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5124-460: Is the main selective reason for outcrossing. Crossbreeding between populations sometimes has positive effects on fitness-related traits, but also sometimes leads to negative effects known as outbreeding depression . However, increased homozygosity increases the probability of fixing beneficial alleles and also slightly decreases the probability of fixing deleterious alleles in a population. Inbreeding can result in purging of deleterious alleles from

5246-500: Is the percentage expressed frequency with which individuals of a given genotype manifest at least some degree of a specific mutant phenotype associated with a trait. Inbreeding , or mating between closely related organisms, can clearly be seen on pedigree charts. Pedigree charts of royal families often have a high degree of inbreeding, because it was customary and preferable for royalty to marry another member of royalty. Genetic counselors commonly use pedigrees to help couples determine if

5368-494: Is the production of offspring from the mating or breeding of individuals or organisms that are closely related genetically . By analogy, the term is used in human reproduction , but more commonly refers to the genetic disorders and other consequences that may arise from expression of deleterious recessive traits resulting from incestuous sexual relationships and consanguinity . Animals avoid inbreeding only rarely. Inbreeding results in homozygosity which can increase

5490-410: Is the study of chromosomes and chromosome abnormalities . While cytogenetics historically relied on microscopy to analyze chromosomes, new molecular technologies such as array comparative genomic hybridization are now becoming widely used. Examples of chromosome abnormalities include aneuploidy , chromosomal rearrangements , and genomic deletion/duplication disorders. Molecular genetics involves

5612-448: Is unlikely that two unrelated partners will both be carriers of the same deleterious allele; however, because close relatives share a large fraction of their alleles, the probability that any such deleterious allele is inherited from the common ancestor through both parents is increased dramatically. For each homozygous recessive individual formed there is an equal chance of producing a homozygous dominant individual — one completely devoid of

5734-570: The Crater lions, it is known that a population bottleneck has occurred. Researchers found far greater genetic heterozygosity than expected. In fact, predators are known for low genetic variance, along with most of the top portion of the trophic levels of an ecosystem . Additionally, the alpha males of two neighboring prides can be from the same litter; one brother may come to acquire leadership over another's pride, and subsequently mate with his 'nieces' or cousins. However, killing another male's cubs, upon

5856-563: The DNA of non-viable human embryos using CRISPR. In February 2016, British scientists were given permission by regulators to genetically modify human embryos by using CRISPR and related techniques on condition that the embryos were destroyed within seven days. In June 2016 the Dutch government was reported to be planning to follow suit with similar regulations which would specify a 14-day limit. The more empirical approach to human and medical genetics

5978-455: The Human Genome Project was able to sequence all the DNA in the human genome, and to discover that the human genome was composed of around 20,000 protein coding genes. Medical genetics is the branch of medicine that involves the diagnosis and management of hereditary disorders . Medical genetics is the application of genetics to medical care. It overlaps human genetics, for example, research on

6100-615: The South American sea lion , there was concern that recent population crashes would reduce genetic diversity. Historical analysis indicated that a population expansion from just two matrilineal lines was responsible for most of the individuals within the population. Even so, the diversity within the lines allowed great variation in the gene pool that may help to protect the South American sea lion from extinction. In lions, prides are often followed by related males in bachelor groups. When

6222-569: The recombination load , and allowing the expression of recessive advantageous phenotypes. Some species with a Haplodiploidy mating system depend on the ability to produce sons to mate with as a means of ensuring a mate can be found if no other male is available. It has been proposed that under circumstances when the advantages of inbreeding outweigh the disadvantages, preferential breeding within small groups could be promoted, potentially leading to speciation . Autosomal recessive disorders occur in individuals who have two copies of an allele for

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6344-401: The sex of an individual is determined by a pair of sex chromosomes ( gonosomes ). Females have two of the same kind of sex chromosome (XX), and are called the homogametic sex . Males have two distinct sex chromosomes (XY), and are called the heterogametic sex . Sex linkage is the phenotypic expression of an allele related to the chromosomal sex of the individual. This mode of inheritance

6466-445: The "power houses" of a cell, have their own DNA. Mitochondria are inherited from one's mother, and their DNA is frequently used to trace maternal lines of descent (see mitochondrial Eve ). Mitochondrial DNA is only 16kb in length and encodes for 62 genes. The XY sex-determination system is the sex-determination system found in humans , most other mammals , some insects ( Drosophila ), and some plants ( Ginkgo ). In this system,

6588-414: The 21st century. The clinical setting in which patients are evaluated determines the scope of practice, diagnostic, and therapeutic interventions. For the purposes of general discussion, the typical encounters between patients and genetic practitioners may involve: Each patient will undergo a diagnostic evaluation tailored to their own particular presenting signs and symptoms. The geneticist will establish

6710-663: The ABMGG. Individuals seeking acceptance into clinical genetics training programs must hold an M.D. or D.O. degree (or their equivalent) and have completed a minimum of 12 months of training in an ACGME -accredited residency program in internal medicine , pediatrics , obstetrics and gynecology , or other medical specialty. In Australia and New Zealand , clinical genetics is a three-year advanced training program for those who already have their primary medical qualification ( MBBS or MD ) and have successfully completed basic training in either paediatric medicine or adult medicine . Training

6832-541: The British Queen Victoria or King Christian IX of Denmark . The House of Habsburg was known for its intermarriages; the Habsburg lip often cited as an ill-effect. The closely related houses of Habsburg, Bourbon , Braganza and Wittelsbach also frequently engaged in first-cousin unions as well as the occasional double-cousin and uncle–niece marriages. In ancient Egypt , royal women were believed to carry

6954-475: The Qatari population suffered from hereditary hearing loss; most were descendants of a consanguineous relationship. Inter-nobility marriage was used as a method of forming political alliances among elites. These ties were often sealed only upon the birth of progeny within the arranged marriage . Thus marriage was seen as a union of lines of nobility and not as a contract between individuals. Royal intermarriage

7076-639: The U.S., medical genetics has its own approved board (the American Board of Medical Genetics) and clinical specialty college (the American College of Medical Genetics ). The college holds an annual scientific meeting, publishes a monthly journal, Genetics in Medicine , and issues position papers and clinical practice guidelines on a variety of topics relevant to human genetics. In Australia and New Zealand , medical geneticists are trained and certified under

7198-457: The US, the newborn screen incorporates biochemical tests to screen for treatable conditions such as galactosemia and phenylketonuria (PKU). Patients suspected to have a metabolic condition might undergo the following tests: Each cell of the body contains the hereditary information ( DNA ) wrapped up in structures called chromosomes . Since genetic syndromes are typically the result of alterations of

7320-500: The ability of the enzyme to reach the affected areas (the blood brain barrier prevents enzyme from reaching the brain, for example), and can sometimes be associated with allergic reactions. The long-term clinical effectiveness of enzyme replacement therapies vary widely among different disorders. There are a variety of career paths within the field of medical genetics, and naturally the training required for each area differs considerably. The information included in this section applies to

7442-425: The abstention from inbreeding. Along with cultural taboos, parental education and awareness of inbreeding consequences have played large roles in minimizing inbreeding frequencies in areas like Europe. That being so, there are less urbanized and less populated regions across the world that have shown continuity in the practice of inbreeding. The continuity of inbreeding is often either by choice or unavoidably due to

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7564-420: The auspices of the Royal Australasian College of Physicians , but professionally belong to the Human Genetics Society of Australasia and its special interest group, the Australasian Association of Clinical Geneticists , for ongoing education, networking and advocacy. The broad range of research in medical genetics reflects the overall scope of this field, including basic research on genetic inheritance and

7686-527: The bloodlines and so it was advantageous for a pharaoh to marry his sister or half-sister; in such cases a special combination between endogamy and polygamy is found. Normally, the old ruler's eldest son and daughter (who could be either siblings or half-siblings) became the new rulers. All rulers of the Ptolemaic dynasty uninterruptedly from Ptolemy IV ( Ptolemy II married his sister but had no issue) were married to their brothers and sisters, so as to keep

7808-491: The causes and inheritance of genetic disorders would be considered within both human genetics and medical genetics, while the diagnosis, management, and counseling of individuals with genetic disorders would be considered part of medical genetics. Population genetics is the branch of evolutionary biology responsible for investigating processes that cause changes in allele and genotype frequencies in populations based upon Mendelian inheritance . Four different forces can influence

7930-694: The causes and inheritance of genetic disorders. Examples of conditions that fall within the scope of medical genetics include birth defects and dysmorphology , intellectual disabilities , autism , mitochondrial disorders, skeletal dysplasia , connective tissue disorders , cancer genetics, and prenatal diagnosis . Medical genetics is increasingly becoming relevant to many common diseases. Overlaps with other medical specialties are beginning to emerge, as recent advances in genetics are revealing etiologies for morphologic , endocrine , cardiovascular , pulmonary , ophthalmologist , renal , psychiatric , and dermatologic conditions. The medical genetics community

8052-517: The chance for these recessive alleles to pair and become homozygous greatly increases, leading to offspring with autosomal recessive disorders. However, these deleterious effects are common for very close relatives but not for those related on the 3rd cousin or greater level, who exhibit increased fitness. Inbreeding is especially problematic in small populations where the genetic variation is already limited. By inbreeding, individuals are further decreasing genetic variation by increasing homozygosity in

8174-477: The chances of offspring being affected by recessive traits . In extreme cases, this usually leads to at least temporarily decreased biological fitness of a population (called inbreeding depression ), which is its ability to survive and reproduce. An individual who inherits such deleterious traits is colloquially referred to as inbred . The avoidance of expression of such deleterious recessive alleles caused by inbreeding, via inbreeding avoidance mechanisms,

8296-472: The chances of the expression of deleterious or beneficial recessive alleles and therefore has the potential to either decrease or increase the fitness of the offspring. Depending on the rate of inbreeding, natural selection may still be able to eliminate deleterious alleles. With continuous inbreeding, genetic variation is lost and homozygosity is increased, enabling the expression of recessive deleterious alleles in homozygotes. The coefficient of inbreeding , or

8418-439: The cheetah went through a population bottleneck that reduced its population dramatically so the animals that are alive today are all related to one another. A consequence from inbreeding for this species has been high juvenile mortality, low fecundity, and poor breeding success. In a study on an island population of song sparrows, individuals that were inbred showed significantly lower survival rates than outbred individuals during

8540-401: The chromosomes or genes, there is no treatment currently available that can correct the genetic alterations in every cell of the body. Therefore, there is currently no "cure" for genetic disorders. However, for many genetic syndromes there is treatment available to manage the symptoms. In some cases, particularly inborn errors of metabolism , the mechanism of disease is well understood and offers

8662-413: The chromosomes to fluoresce a unique color. Genomics is the field of genetics concerned with structural and functional studies of the genome. A genome is all the DNA contained within an organism or a cell including nuclear and mitochondrial DNA. The human genome is the total collection of genes in a human being contained in the human chromosome, composed of over three billion nucleotides. In April 2003,

8784-444: The closest available mate is a mother, sister, grandmother, father, brother, or grandfather. In all cases, the environment presents stresses to remove from the population those individuals who cannot survive because of illness. There was an assumption that wild populations do not inbreed; this is not what is observed in some cases in the wild. However, in species such as horses , animals in wild or feral conditions often drive off

8906-424: The degree of inbreeding in an individual, is an estimate of the percent of homozygous alleles in the overall genome. The more biologically related the parents are, the greater the coefficient of inbreeding, since their genomes have many similarities already. This overall homozygosity becomes an issue when there are deleterious recessive alleles in the gene pool of the family. By pairing chromosomes of similar genomes,

9028-421: The diagnosis and management of mitochondrial disorders, which have a molecular basis but often result in biochemical abnormalities due to deficient energy production. There exists some overlap between medical genetic diagnostic laboratories and molecular pathology . Genetic counseling is the process of providing information about genetic conditions, diagnostic testing, and risks in other family members, within

9150-577: The discovery of and laboratory testing for DNA mutations that underlie many single gene disorders . Examples of single gene disorders include achondroplasia , cystic fibrosis , Duchenne muscular dystrophy , hereditary breast cancer (BRCA1/2), Huntington disease , Marfan syndrome , Noonan syndrome , and Rett syndrome . Molecular tests are also used in the diagnosis of syndromes involving epigenetic abnormalities, such as Angelman syndrome , Beckwith-Wiedemann syndrome , Prader-willi syndrome , and uniparental disomy . Mitochondrial genetics concerns

9272-399: The dominant male is killed or driven off by one of these bachelors, a father may be replaced by his son. There is no mechanism for preventing inbreeding or to ensure outcrossing. In the prides, most lionesses are related to one another. If there is more than one dominant male, the group of alpha males are usually related. Two lines are then being "line bred". Also, in some populations, such as

9394-647: The enzyme is made but is not functioning properly), inhibition of other enzymes in the biochemical pathway to prevent buildup of a toxic compound, or diversion of a toxic compound to another form that can be excreted. Examples include the use of high doses of pyridoxine (vitamin B6) in some patients with homocystinuria to boost the activity of the residual cystathione synthase enzyme, administration of biotin to restore activity of several enzymes affected by deficiency of biotinidase , treatment with NTBC in Tyrosinemia to inhibit

9516-433: The excess of "E" which is normally only present in small amounts and only accumulates when "C" is in excess. Treatment of the metabolic disorder could be achieved through dietary supplementation of compound "D" and dietary restriction of compounds "A", "B", and/or "C" or by treatment with a medication that promoted disposal of excess "A", "B", "C" or "E". Another approach that can be taken is enzyme replacement therapy, in which

9638-405: The expression of genes that allow a population to adapt to an ecosystem . As the adaptation becomes more pronounced, the new species or race radiates from its entrance into the new space, or dies out if it cannot adapt and, most importantly, reproduce. The reduced genetic diversity , for example due to a bottleneck will unavoidably increase inbreeding for the entire population. This may mean that

9760-459: The extent to which patterns of genetic variation influence group differences in health outcomes. According to the common disease/common variant hypothesis, common variants present in the ancestral population before the dispersal of modern humans from Africa play an important role in human diseases. Genetic variants associated with Alzheimer disease, deep venous thrombosis, Crohn disease, and type 2 diabetes appear to adhere to this model. However,

9882-561: The foundational medical knowledge required to specialize in Medical Genetics. The optimal training program involves a total of five years: one year of general medical training (the "common trunk", often covering fields such as general practice, pediatrics, obstetrics and gynecology, neurology, psychiatry, and internal medicine) followed by four years of specialized training in Medical Genetics. This specialized training should include at least two years of clinical patient care and at least six months in genetic laboratory diagnostics. Trainees' progress

10004-522: The framework of nondirective counseling. Genetic counselors are non-physician members of the medical genetics team who specialize in family risk assessment and counseling of patients regarding genetic disorders. The precise role of the genetic counselor varies somewhat depending on the disorder. When working alongside geneticists, genetic counselors normally specialize in pediatric genetics which focuses on developmental abnormalities present in newborns, infants or children. The major goal of pediatric counseling

10126-476: The frequencies: natural selection , mutation , gene flow (migration), and genetic drift . A population can be defined as a group of interbreeding individuals and their offspring. For human genetics the populations will consist only of the human species. The Hardy–Weinberg principle is a widely used principle to determine allelic and genotype frequencies. In addition to nuclear DNA , humans (like almost all eukaryotes ) have mitochondrial DNA . Mitochondria ,

10248-400: The general population. Children of parent-child or sibling-sibling unions are at an increased risk compared to cousin-cousin unions. Inbreeding may result in a greater than expected phenotypic expression of deleterious recessive alleles within a population. As a result, first-generation inbred individuals are more likely to show physical and health defects, including: The isolation of

10370-692: The generality of the model has not yet been established and, in some cases, is in doubt. Some diseases, such as many common cancers, appear not to be well described by the common disease/common variant model. Another possibility is that common diseases arise in part through the action of combinations of variants that are individually rare. Most of the disease-associated alleles discovered to date have been rare, and rare variants are more likely than common variants to be differentially distributed among groups distinguished by ancestry. However, groups could harbor different, though perhaps overlapping, sets of rare variants, which would reduce contrasts between groups in

10492-409: The genetic diversity of a population and cause problems related to a too-small gene pool that may include an increased prevalence of genetic disorders and inbreeding depression. Outcrossing is where two unrelated individuals are crossed to produce progeny. In outcrossing, unless there is verifiable genetic information, one may find that all individuals are distantly related to an ancient progenitor. If

10614-460: The genetics of DNA repair defects related to accelerated aging and/or increased risk of cancer please see: DNA repair-deficiency disorder . Inheritance of traits for humans are based upon Gregor Mendel 's model of inheritance. Mendel deduced that inheritance depends upon discrete units of inheritance, called factors or genes. Autosomal traits are associated with a single gene on an autosome (non-sex chromosome)—they are called " dominant " because

10736-411: The genomes of their offspring. Thus, the likelihood of deleterious recessive alleles to pair is significantly higher in a small inbreeding population than in a larger inbreeding population. The fitness consequences of consanguineous mating have been studied since their scientific recognition by Charles Darwin in 1839. Some of the most harmful effects known from such breeding includes its effects on

10858-412: The harmful allele. Contrary to common belief, inbreeding does not in itself alter allele frequencies, but rather increases the relative proportion of homozygotes to heterozygotes; however, because the increased proportion of deleterious homozygotes exposes the allele to natural selection , in the long run its frequency decreases more rapidly in inbred populations. In the short term, incestuous reproduction

10980-435: The human genome, mechanisms of genetic and metabolic disorders, translational research on new treatment modalities, and the impact of genetic testing Basic research geneticists usually undertake research in universities, biotechnology firms and research institutes. Sometimes the link between a disease and an unusual gene variant is more subtle. The genetic architecture of common diseases is an important factor in determining

11102-495: The hypothetical example: Compound "A" is metabolized to "B" by enzyme "X", compound "B" is metabolized to "C" by enzyme "Y", and compound "C" is metabolized to "D" by enzyme "Z". If enzyme "Z" is missing, compound "D" will be missing, while compounds "A", "B", and "C" will build up. The pathogenesis of this particular condition could result from lack of compound "D", if it is critical for some cellular function, or from toxicity due to excess "A", "B", and/or "C", or from toxicity due to

11224-506: The inbreeding and the coancestry coefficients can be defined for specific individuals or as average population values. They can be computed from genealogies or estimated from the population size and its breeding properties, but all methods assume no selection and are limited to neutral alleles. There are several methods to compute this percentage. The two main ways are the path method and the tabular method. Typical coancestries between relatives are as follows: Breeding in domestic animals

11346-429: The incidence of the disease. The number of variants contributing to a disease and the interactions among those variants also could influence the distribution of diseases among groups. The difficulty that has been encountered in finding contributory alleles for complex diseases and in replicating positive associations suggests that many complex diseases involve numerous variants rather than a moderate number of alleles, and

11468-406: The influence of any given variant may depend in critical ways on the genetic and environmental background. If many alleles are required to increase susceptibility to a disease, the odds are low that the necessary combination of alleles would become concentrated in a particular group purely through drift. One area in which population categories can be important considerations in genetics research

11590-405: The karyotype can be used to detect deletions , insertions , duplications, inversions, and translocations . G-banding will stain the chromosomes with light and dark bands unique to each chromosome. A FISH, fluorescent in situ hybridization , can be used to observe deletions, insertions, and translocations. FISH uses fluorescent probes to bind to specific sequences of the chromosomes that will cause

11712-701: The limitations of the geographical area. When by choice, the rate of consanguinity is highly dependent on religion and culture. In the Western world, some Anabaptist groups are highly inbred because they originate from small founder populations that have bred as a closed population. Of the practicing regions, Middle Eastern and northern Africa territories show the greatest frequencies of consanguinity. Among these populations with high levels of inbreeding, researchers have found several disorders prevalent among inbred offspring. In Lebanon , Saudi Arabia , Egypt , and in Israel ,

11834-550: The mortality rate as well as on the general health of the offspring. Since the 1960s, there have been many studies to support such debilitating effects on the human organism. Specifically, inbreeding has been found to decrease fertility as a direct result of increasing homozygosity of deleterious recessive alleles. Fetuses produced by inbreeding also face a greater risk of spontaneous abortions due to inherent complications in development. Among mothers who experience stillbirths and early infant deaths, those that are inbreeding have

11956-413: The mother will show up. Females express X-linked disorders when they are homozygous for the disorder and become carriers when they are heterozygous. X-linked dominant inheritance will show the same phenotype as a heterozygote and homozygote. Just like X-linked inheritance, there will be a lack of male-to-male inheritance, which makes it distinguishable from autosomal traits. One example of an X-linked trait

12078-473: The negative health consequences of excessive inbreeding. Linebreeding is a form of inbreeding. There is no clear distinction between the two terms, but linebreeding may encompass crosses between individuals and their descendants or two cousins. This method can be used to increase a particular animal's contribution to the population. While linebreeding is less likely to cause problems in the first generation than does inbreeding, over time, linebreeding can reduce

12200-563: The offspring of consanguineous relationships have an increased risk of congenital malformations, congenital heart defects, congenital hydrocephalus and neural tube defects . Furthermore, among inbred children in Palestine and Lebanon, there is a positive association between consanguinity and reported cleft lip/palate cases. Historically, populations of Qatar have engaged in consanguineous relationships of all kinds, leading to high risk of inheriting genetic diseases. As of 2014, around 5% of

12322-489: The parents will be able to produce healthy children. A karyotype is a very useful tool in cytogenetics. A karyotype is picture of all the chromosomes in the metaphase stage arranged according to length and centromere position. A karyotype can also be useful in clinical genetics, due to its ability to diagnose genetic disorders. On a normal karyotype, aneuploidy can be detected by clearly being able to observe any missing or extra chromosomes. Giemsa banding, g-banding , of

12444-417: The patient and family to maintain, and require close consultation with a nutritionist who has special experience in metabolic disorders. The composition of the diet will change depending on the caloric needs of the growing child and special attention is needed during a pregnancy if a woman is affected with one of these disorders. Medical approaches include enhancement of residual enzyme activity (in cases where

12566-573: The patient. Although genetics has its roots back in the 19th century with the work of the Bohemian monk Gregor Mendel and other pioneering scientists, human genetics emerged later. It started to develop, albeit slowly, during the first half of the 20th century. Mendelian (single-gene) inheritance was studied in a number of important disorders such as albinism, brachydactyly (short fingers and toes), and hemophilia . Mathematical approaches were also devised and applied to human genetics. Population genetics

12688-572: The population should also be considered when discussing the variation in the severity of inbreeding depression between and within species. With persistent inbreeding, there is evidence that shows that inbreeding depression becomes less severe. This is associated with the unmasking and elimination of severely deleterious recessive alleles. However, inbreeding depression is not a temporary phenomenon because this elimination of deleterious recessive alleles will never be complete. Eliminating slightly deleterious mutations through inbreeding under moderate selection

12810-438: The possible effects of inbreeding, such as congenital birth defects . The chances of such disorders are increased when the biological parents are more closely related. This is because such pairings have a 25% probability of producing homozygous zygotes, resulting in offspring with two recessive alleles , which can produce disorders when these alleles are deleterious. Because most recessive alleles are rare in populations, it

12932-415: The potential for dietary and medical management to prevent or reduce the long-term complications. In other cases, infusion therapy is used to replace the missing enzyme. Current research is actively seeking to use gene therapy or other new medications to treat specific genetic disorders. In general, metabolic disorders arise from enzyme deficiencies that disrupt normal metabolic pathways. For instance, in

13054-490: The production of succinylacetone which causes liver toxicity, and the use of sodium benzoate to decrease ammonia build-up in urea cycle disorders . Certain lysosomal storage diseases are treated with infusions of a recombinant enzyme (produced in a laboratory), which can reduce the accumulation of the compounds in various tissues. Examples include Gaucher disease , Fabry disease , Mucopolysaccharidoses and Glycogen storage disease type II . Such treatments are limited by

13176-440: The rate of casual inbreeding. Many of the traits that affect profitability in crosses of modern dairy breeds have not been studied in designed experiments. Indeed, all crossbreeding research involving North American breeds and strains is very dated (McAllister, 2001) if it exists at all. The BBC produced two documentaries on dog inbreeding titled Pedigree Dogs Exposed and Pedigree Dogs Exposed: Three Years On that document

13298-511: The same allele in an ancestor. These two identical alleles that are both derived from a common ancestor are said to be identical by descent . This probability F(A) is called the " coefficient of inbreeding ". Another useful measure that describes the extent to which two individuals are related (say individuals A and B) is their coancestry coefficient f(A,B), which gives the probability that one randomly selected allele from A and another randomly selected allele from B are identical by descent. This

13420-545: The sex X chromosome. X-linked genes just like autosomal genes have both dominant and recessive types. Recessive X-linked disorders are rarely seen in females and usually only affect males. This is because males inherit their X chromosome and all X-linked genes will be inherited from the maternal side. Fathers only pass on their Y chromosome to their sons, so no X-linked traits will be inherited from father to son. Men cannot be carriers for recessive X linked traits, as they only have one X chromosome, so any X linked trait inherited from

13542-465: The specialty across Europe and is increasingly recognized by various national regulatory authorities. In the United States , physicians who practice clinical genetics are accredited by the American Board of Medical Genetics and Genomics (ABMGG). In order to become a board-certified practitioner of Clinical Genetics, a physician must complete a minimum of 24 months of training in a program accredited by

13664-618: The study of typically non-medical phenotypes such as the genetics of eye color would be considered part of human genetics, but not necessarily relevant to medical genetics (except in situations such as albinism ). Genetic medicine is a newer term for medical genetics and incorporates areas such as gene therapy , personalized medicine , and the rapidly emerging new medical specialty, predictive medicine . Medical genetics encompasses many different areas, including clinical practice of physicians, genetic counselors, and nutritionists, clinical diagnostic laboratory activities, and research into

13786-455: The takeover, allows the new selected gene complement of the incoming alpha male to prevail over the previous male. There are genetic assays being scheduled for lions to determine their genetic diversity. The preliminary studies show results inconsistent with the outcrossing paradigm based on individual environments of the studied groups. In Central California, sea otters were thought to have been driven to extinction due to over hunting, until

13908-694: The training of physicians in Clinical/Medical Genetics is overseen by the Union Européenne des Médecins Spécialistes (UEMS) . This organization aims to harmonize and raise the standards of medical specialist training across Europe. The UEMS has established European Training Requirements (ETR) for Medical Genetics to guide the education and training of medical geneticists. Individuals seeking acceptance into clinical genetics training programs must hold an MD , or in some countries, an MB ChB or MB BS degree. These qualifications ensure that trainees have

14030-408: The trait carries throughout a population, all individuals can have this trait. This is called the founder effect . In the well established breeds, that are commonly bred, a large gene pool is present. For example, in 2004, over 18,000 Persian cats were registered. A possibility exists for a complete outcross, if no barriers exist between the individuals to breed. However, it is not always the case, and

14152-425: The transfer of deleterious alleles may be achieved by reproductive isolation, sterilization , or, in the extreme case, culling . Culling is not strictly necessary if genetics are the only issue in hand. Small animals such as cats and dogs may be sterilized, but in the case of large agricultural animals, such as cattle, culling is usually the only economic option. The issue of casual breeders who inbreed irresponsibly

14274-558: The type of gene action affecting a trait. Inbreeding is also used to reveal deleterious recessive alleles, which can then be eliminated through assortative breeding or through culling. In plant breeding , inbred lines are used as stocks for the creation of hybrid lines to make use of the effects of heterosis . Inbreeding in plants also occurs naturally in the form of self-pollination . Inbreeding can significantly influence gene expression which can prevent inbreeding depression. Offspring of biologically related persons are subject to

14396-529: The typical pathways in the United States and there may be differences in other countries. US practitioners in clinical, counseling, or diagnostic subspecialties generally obtain board certification through the American Board of Medical Genetics . Genetic information provides a unique type of knowledge about an individual and his/her family, fundamentally different from a typically laboratory test that provides

14518-439: The young of both sexes, thought to be a mechanism by which the species instinctively avoids some of the genetic consequences of inbreeding. In general, many mammal species, including humanity's closest primate relatives, avoid close inbreeding possibly due to the deleterious effects. Although there are several examples of inbred populations of wild animals, the negative consequences of this inbreeding are poorly documented. In

14640-428: Was created. Medical genetics was a late developer, emerging largely after the close of World War II (1945) when the eugenics movement had fallen into disrepute. The Nazi misuse of eugenics sounded its death knell. Shorn of eugenics, a scientific approach could be used and was applied to human and medical genetics. Medical genetics saw an increasingly rapid rise in the second half of the 20th century and continues in

14762-606: Was formalized by the founding in 1948 of the American Society of Human Genetics . The Society first began annual meetings that year (1948) and its international counterpart, the International Congress of Human Genetics , has met every 5 years since its inception in 1956. The Society publishes the American Journal of Human Genetics on a monthly basis. Medical genetics is recognized as a distinct medical specialty. In

14884-423: Was often practiced among European royal families, usually for interests of state. Over time, due to the relatively limited number of potential consorts, the gene pool of many ruling families grew progressively smaller, until all European royalty was related. This also resulted in many being descended from a certain person through many lines of descent, such as the numerous European royalty and nobility descended from

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