92-451: 1IC8 , 2GYP 6927 21405 ENSG00000135100 ENSMUSG00000029556 P20823 P22361 NM_000545 NM_001306179 NM_009327 NP_000536 NP_001293108 NP_000536.5 NP_001293108.1 NP_033353 HNF1 homeobox A (hepatocyte nuclear factor 1 homeobox A), also known as HNF1A , is a human gene on chromosome 12 . It is ubiquitously expressed in many tissues and cell types. The protein encoded by this gene
184-584: A promoter sequence. The promoter is recognized and bound by transcription factors that recruit and help RNA polymerase bind to the region to initiate transcription. The recognition typically occurs as a consensus sequence like the TATA box . A gene can have more than one promoter, resulting in messenger RNAs ( mRNA ) that differ in how far they extend in the 5' end. Highly transcribed genes have "strong" promoter sequences that form strong associations with transcription factors, thereby initiating transcription at
276-512: A " start codon ", and three " stop codons " indicate the beginning and end of the protein coding region . There are 64 possible codons (four possible nucleotides at each of three positions, hence 4 possible codons) and only 20 standard amino acids; hence the code is redundant and multiple codons can specify the same amino acid. The correspondence between codons and amino acids is nearly universal among all known living organisms. Intestinal epithelium The intestinal epithelium
368-452: A community cohort study (the Malmo Diet and Cancer study) and four additional randomized controlled trials of primary prevention cohorts (JUPITER and ASCOT) and secondary prevention cohorts (CARE and PROVE IT-TIMI 22). HNF1A has been shown to interact with: Gene In biology , the word gene has two meanings. The Mendelian gene is a basic unit of heredity . The molecular gene is
460-519: A complex anatomical structure which facilitates motility and coordinated digestive, absorptive, immunological and neuroendocrine functions. The mucus secreted by goblet cells acts as a lubricant and protects the epithelial cell layer against irritation from mucosal contents. Traditionally, crypt cells were considered primarily as secretory cells while enterocytes are considered principally absorptive. However, recent studies have challenged this classical functional partitioning and have shown that both
552-445: A continuous messenger RNA , referred to as a polycistronic mRNA . The term cistron in this context is equivalent to gene. The transcription of an operon's mRNA is often controlled by a repressor that can occur in an active or inactive state depending on the presence of specific metabolites. When active, the repressor binds to a DNA sequence at the beginning of the operon, called the operator region , and represses transcription of
644-495: A double-helix run in opposite directions. Nucleic acid synthesis, including DNA replication and transcription occurs in the 5'→3' direction, because new nucleotides are added via a dehydration reaction that uses the exposed 3' hydroxyl as a nucleophile . The expression of genes encoded in DNA begins by transcribing the gene into RNA , a second type of nucleic acid that is very similar to DNA, but whose monomers contain
736-488: A few genes and are transferable between individuals. For example, the genes for antibiotic resistance are usually encoded on bacterial plasmids and can be passed between individual cells, even those of different species, via horizontal gene transfer . Whereas the chromosomes of prokaryotes are relatively gene-dense, those of eukaryotes often contain regions of DNA that serve no obvious function. Simple single-celled eukaryotes have relatively small amounts of such DNA, whereas
828-434: A gene - surprisingly, there is no definition that is entirely satisfactory. A gene is a DNA sequence that codes for a diffusible product. This product may be protein (as is the case in the majority of genes) or may be RNA (as is the case of genes that code for tRNA and rRNA). The crucial feature is that the product diffuses away from its site of synthesis to act elsewhere. The important parts of such definitions are: (1) that
920-565: A gene corresponds to a transcription unit; (2) that genes produce both mRNA and noncoding RNAs; and (3) regulatory sequences control gene expression but are not part of the gene itself. However, there's one other important part of the definition and it is emphasized in Kostas Kampourakis' book Making Sense of Genes . Therefore in this book I will consider genes as DNA sequences encoding information for functional products, be it proteins or RNA molecules. With 'encoding information', I mean that
1012-410: A gene may be split across chromosomes but those transcripts are concatenated back together into a functional sequence by trans-splicing . It is also possible for overlapping genes to share some of their DNA sequence, either on opposite strands or the same strand (in a different reading frame, or even the same reading frame). In all organisms, two steps are required to read the information encoded in
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#17330860502371104-404: A gene's DNA and produce the protein it specifies. First, the gene's DNA is transcribed to messenger RNA ( mRNA ). Second, that mRNA is translated to protein. RNA-coding genes must still go through the first step, but are not translated into protein. The process of producing a biologically functional molecule of either RNA or protein is called gene expression , and the resulting molecule
1196-565: A gene: that of bacteriophage MS2 coat protein. The subsequent development of chain-termination DNA sequencing in 1977 by Frederick Sanger improved the efficiency of sequencing and turned it into a routine laboratory tool. An automated version of the Sanger method was used in early phases of the Human Genome Project . The theories developed in the early 20th century to integrate Mendelian genetics with Darwinian evolution are called
1288-439: A gene; however, members of a population may have different alleles at the locus, each with a slightly different gene sequence. The majority of eukaryotic genes are stored on a set of large, linear chromosomes. The chromosomes are packed within the nucleus in complex with storage proteins called histones to form a unit called a nucleosome . DNA packaged and condensed in this way is called chromatin . The manner in which DNA
1380-448: A high rate. Others genes have "weak" promoters that form weak associations with transcription factors and initiate transcription less frequently. Eukaryotic promoter regions are much more complex and difficult to identify than prokaryotic promoters. Additionally, genes can have regulatory regions many kilobases upstream or downstream of the gene that alter expression. These act by binding to transcription factors which then cause
1472-572: A new expanded definition that includes noncoding genes. However, some modern writers still do not acknowledge noncoding genes although this so-called "new" definition has been recognised for more than half a century. Although some definitions can be more broadly applicable than others, the fundamental complexity of biology means that no definition of a gene can capture all aspects perfectly. Not all genomes are DNA (e.g. RNA viruses ), bacterial operons are multiple protein-coding regions transcribed into single large mRNAs, alternative splicing enables
1564-400: A process known as RNA splicing . Finally, the ends of gene transcripts are defined by cleavage and polyadenylation (CPA) sites , where newly produced pre-mRNA gets cleaved and a string of ~200 adenosine monophosphates is added at the 3' end. The poly(A) tail protects mature mRNA from degradation and has other functions, affecting translation, localization, and transport of the transcript from
1656-419: A protein-coding gene consists of many elements of which the actual protein coding sequence is often only a small part. These include introns and untranslated regions of the mature mRNA. Noncoding genes can also contain introns that are removed during processing to produce the mature functional RNA. All genes are associated with regulatory sequences that are required for their expression. First, genes require
1748-481: A sequence of nucleotides in DNA that is transcribed to produce a functional RNA . There are two types of molecular genes: protein-coding genes and non-coding genes. During gene expression (the synthesis of RNA or protein from a gene), DNA is first copied into RNA . RNA can be directly functional or be the intermediate template for the synthesis of a protein. The transmission of genes to an organism's offspring ,
1840-412: A single genomic region to encode multiple district products and trans-splicing concatenates mRNAs from shorter coding sequence across the genome. Since molecular definitions exclude elements such as introns, promotors, and other regulatory regions , these are instead thought of as "associated" with the gene and affect its function. An even broader operational definition is sometimes used to encompass
1932-472: A strict definition of the word "gene" with which nearly every expert can agree. First, in order for a nucleotide sequence to be considered a true gene, an open reading frame (ORF) must be present. The ORF can be thought of as the "gene itself"; it begins with a starting mark common for every gene and ends with one of three possible finish line signals. One of the key enzymes in this process, the RNA polymerase, zips along
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#17330860502372024-409: A true gene, by this definition, one has to prove that the transcript has a biological function. Early speculations on the size of a typical gene were based on high-resolution genetic mapping and on the size of proteins and RNA molecules. A length of 1500 base pairs seemed reasonable at the time (1965). This was based on the idea that the gene was the DNA that was directly responsible for production of
2116-547: Is a transcription factor that is highly expressed in the liver and is involved in the regulation of the expression of several liver-specific genes. Mutations in the HNF1A gene have been known to cause diabetes . The HNF1A gene also contains a SNP associated with increased risk of coronary artery disease . The HNF1A gene resides on chromosome 12 at the band 12q24.2 and contains 10 exons . This gene produces 8 isoforms through alternative splicing . This protein belongs to
2208-452: Is also associated with risk of developing type 2 diabetes and increased penetrance of early-onset diabetes A multi-locus genetic risk score study based on a combination of 27 loci, including the HNF1A gene, identified individuals at increased risk for both incident and recurrent coronary artery disease events, as well as an enhanced clinical benefit from statin therapy. The study was based on
2300-457: Is an important cell-intrinsic transcription factor in adult B lymphopoiesis . The participation of HNF-1α in glucose metabolism and diabetes has been reported, including the involvement in GLUT1 and GLUT2 transporter expression in pancreatic β-cells and angiotensin-converting enzyme 2 gene expression in pancreatic islets . HNF-1α could promote the transcription of several proteins involved in
2392-456: Is called a gene product . The nucleotide sequence of a gene's DNA specifies the amino acid sequence of a protein through the genetic code . Sets of three nucleotides, known as codons , each correspond to a specific amino acid. The principle that three sequential bases of DNA code for each amino acid was demonstrated in 1961 using frameshift mutations in the rIIB gene of bacteriophage T4 (see Crick, Brenner et al. experiment ). Additionally,
2484-670: Is composed of oligosaccharides attached to membrane glycoproteins and glycolipids . Different cell types are produced by the stem cells that reside at the base of the crypts. Each type matures according to its specific differentiation program as it migrates up and out of the crypt. Many of the genes necessary for differentiation into the different epithelial cell types have been identified and characterized. The cell types produced are: enterocytes (small intestine) (known as colonocytes in colon), Goblet cells , enteroendocrine cells , Paneth cells , microfold cells , cup cells and tuft cells . Their functions are listed here: Throughout
2576-400: Is nearly the same for all known organisms. The total complement of genes in an organism or cell is known as its genome , which may be stored on one or more chromosomes . A chromosome consists of a single, very long DNA helix on which thousands of genes are encoded. The region of the chromosome at which a particular gene is located is called its locus . Each locus contains one allele of
2668-403: Is still part of the definition of a gene in most textbooks. For example, The primary function of the genome is to produce RNA molecules. Selected portions of the DNA nucleotide sequence are copied into a corresponding RNA nucleotide sequence, which either encodes a protein (if it is an mRNA) or forms a 'structural' RNA, such as a transfer RNA (tRNA) or ribosomal RNA (rRNA) molecule. Each region of
2760-399: Is stored on the histones, as well as chemical modifications of the histone itself, regulate whether a particular region of DNA is accessible for gene expression . In addition to genes, eukaryotic chromosomes contain sequences involved in ensuring that the DNA is copied without degradation of end regions and sorted into daughter cells during cell division: replication origins , telomeres , and
2852-407: Is the single cell layer that forms the luminal surface (lining) of both the small and large intestine (colon) of the gastrointestinal tract . Composed of simple columnar epithelium its main functions are absorption, and secretion. Useful substances are absorbed into the body, and the entry of harmful substances is restricted. Secretions include mucins , and peptides . Absorptive cells in
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2944-431: Is the basis of the inheritance of phenotypic traits from one generation to the next. These genes make up different DNA sequences, together called a genotype , that is specific to every given individual, within the gene pool of the population of a given species . The genotype, along with environmental and developmental factors, ultimately determines the phenotype of the individual. Most biological traits occur under
3036-706: Is thought to stabilize the interface to improve transcriptional efficiency. Meanwhile, the dimerization domain is responsible for the homo- and heterodimerization of HNF-1α. The resulting dimer contains a rigid “mini-zipper”, comprising α-helices 1 and 1′, linked by a non-canonical tight turn to a flexible C-terminal comprising α-helices 2 and 2′. HNF-1α is a transcription factor expressed in organs of endoderm origin, including liver , kidneys , pancreas , intestines , stomach , spleen , thymus , testis , and keratinocytes and melanocytes in human skin . It has been shown to affect intestinal epithelial cell growth and cell lineages differentiation. For instance, HNF1A
3128-410: The actin cytoskeletons of the cells . Besides their role in linking adjacent cells, these complexes are important for regulating epithelial migration, cell polarity , and the formation of other cell junction complexes. Tight junctions, also called zonula occludens, are the most important components of the intestinal epithelium for its barrier function. These complexes, formed primarily of members of
3220-511: The aging process. The centromere is required for binding spindle fibres to separate sister chromatids into daughter cells during cell division . Prokaryotes ( bacteria and archaea ) typically store their genomes on a single, large, circular chromosome . Similarly, some eukaryotic organelles contain a remnant circular chromosome with a small number of genes. Prokaryotes sometimes supplement their chromosome with additional small circles of DNA called plasmids , which usually encode only
3312-451: The cadherin family, link adjacent cells together through their cytoskeletons . Desmosomes leave a gap of 30 nanometers between cells. Adherens junctions, also called zonula adherens, are multiprotein complexes formed by proteins of the catenin and cadherin families. They are located in the membrane at the contact points between the cells. They are formed by interactions between intracellular adapter proteins, transmembrane proteins and
3404-401: The central dogma of molecular biology , which states that proteins are translated from RNA , which is transcribed from DNA . This dogma has since been shown to have exceptions, such as reverse transcription in retroviruses . The modern study of genetics at the level of DNA is known as molecular genetics . In 1972, Walter Fiers and his team were the first to determine the sequence of
3496-419: The centromere . Replication origins are the sequence regions where DNA replication is initiated to make two copies of the chromosome. Telomeres are long stretches of repetitive sequences that cap the ends of the linear chromosomes and prevent degradation of coding and regulatory regions during DNA replication . The length of the telomeres decreases each time the genome is replicated and has been implicated in
3588-595: The claudin and the occludin families, consist of about 35 different proteins, form a ring shaped continuous ribbon around the cells, and are located near the borders of the lateral and apical membranes. The extracellular domains of the transmembrane proteins in adjacent cells cross connect to form a tight seal. These interactions include those between proteins in the same membrane ("cis") and proteins in adjacent cells ("trans"). In addition, interactions can be homophilic (between identical proteins) or heterophilic (between different proteins). Similar to adherens junctions,
3680-457: The connexin gene family coming together to form a multiprotein complex . The molecular structure of this complex is in the form of a hexamer . The complex, which is embedded in the cell membranes of the two joined cells, forms a gap or channel in the middle of the six proteins. This channel allows various molecules , ions and electrical impulses to pass between the two cells. These complexes, consisting of transmembrane adhesion proteins of
3772-402: The crypt (base) of the intestinal glands (epithelial invaginations into the underlying connective tissue). After being formed at the base, the new cells migrate upwards and out of the crypt, maturing along the way. Eventually, they undergo apoptosis and are shed off into the intestinal lumen. In this way, the lining of the intestine is constantly renewed while the number of cells making up
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3864-424: The epithelial layer remains constant. In the small intestine, the mucosal layer is specially adapted to provide a large surface area in order to maximize the absorption of nutrients. The expansion of the absorptive surface, 600 times beyond that of a simple cylindrical tube, is achieved by three anatomical features: The brush border on the apical surface of the epithelial cells is covered with glycocalyx , which
3956-549: The modern synthesis , a term introduced by Julian Huxley . This view of evolution was emphasized by George C. Williams ' gene-centric view of evolution . He proposed that the Mendelian gene is a unit of natural selection with the definition: "that which segregates and recombines with appreciable frequency." Related ideas emphasizing the centrality of Mendelian genes and the importance of natural selection in evolution were popularized by Richard Dawkins . The development of
4048-475: The neutral theory of evolution in the late 1960s led to the recognition that random genetic drift is a major player in evolution and that neutral theory should be the null hypothesis of molecular evolution. This led to the construction of phylogenetic trees and the development of the molecular clock , which is the basis of all dating techniques using DNA sequences. These techniques are not confined to molecular gene sequences but can be used on all DNA segments in
4140-750: The operon ; when the repressor is inactive transcription of the operon can occur (see e.g. Lac operon ). The products of operon genes typically have related functions and are involved in the same regulatory network . Though many genes have simple structures, as with much of biology, others can be quite complex or represent unusual edge-cases. Eukaryotic genes often have introns that are much larger than their exons, and those introns can even have other genes nested inside them . Associated enhancers may be many kilobase away, or even on entirely different chromosomes operating via physical contact between two chromosomes. A single gene can encode multiple different functional products by alternative splicing , and conversely
4232-449: The population . These alleles encode slightly different versions of a gene, which may cause different phenotypical traits. Genes evolve due to natural selection or survival of the fittest and genetic drift of the alleles. There are many different ways to use the term "gene" based on different aspects of their inheritance, selection, biological function, or molecular structure but most of these definitions fall into two categories,
4324-457: The small intestine are known as enterocytes , and in the colon they are known as colonocytes . The other cell types are the secretory cells – goblet cells , Paneth cells , enteroendocrine cells , and Tuft cells . Paneth cells are absent in the colon. As part of its protective role, the intestinal epithelium forms an important component of the intestinal mucosal barrier . Certain diseases and conditions are caused by functional defects in
4416-404: The DNA helix that produces a functional RNA molecule constitutes a gene. We define a gene as a DNA sequence that is transcribed. This definition includes genes that do not encode proteins (not all transcripts are messenger RNA). The definition normally excludes regions of the genome that control transcription but are not themselves transcribed. We will encounter some exceptions to our definition of
4508-450: The DNA sequence is used as a template for the production of an RNA molecule or a protein that performs some function. The emphasis on function is essential because there are stretches of DNA that produce non-functional transcripts and they do not qualify as genes. These include obvious examples such as transcribed pseudogenes as well as less obvious examples such as junk RNA produced as noise due to transcription errors. In order to qualify as
4600-766: The DNA to loop so that the regulatory sequence (and bound transcription factor) become close to the RNA polymerase binding site. For example, enhancers increase transcription by binding an activator protein which then helps to recruit the RNA polymerase to the promoter; conversely silencers bind repressor proteins and make the DNA less available for RNA polymerase. The mature messenger RNA produced from protein-coding genes contains untranslated regions at both ends which contain binding sites for ribosomes , RNA-binding proteins , miRNA , as well as terminator , and start and stop codons . In addition, most eukaryotic open reading frames contain untranslated introns , which are removed and exons , which are connected together in
4692-467: The HNF1 homeobox family. It contains 3 functional domains: an N-terminal dimerization domain ( residues 1–32), a bipartite DNA-binding motif containing an atypical POU-homeodomain (residues 98–280), and a C-terminal transactivation domain (residues 281–631). There is also a flexible linker (residues 33–97) which connects the dimerization and DNA binding domains . Crystal structures have been solved for
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#17330860502374784-452: The HNF1A gene have been described as sensitive to the hypoglycemic effects of sulphonylureas. The cause of hyperglycemia appears to alter the response to hypoglycemic drugs. Accordingly, HNF-1α-induced diabetes has marked sulphonylurea sensitivity. This pharmacogenetic effect is consistent with models of HNF-1α deficiency, and the genetic basis of hyperglycemia may have implications for patient management. Common genetic variation within HNF1A
4876-506: The Mendelian gene or the molecular gene. The Mendelian gene is the classical gene of genetics and it refers to any heritable trait. This is the gene described in The Selfish Gene . More thorough discussions of this version of a gene can be found in the articles Genetics and Gene-centered view of evolution . The molecular gene definition is more commonly used across biochemistry, molecular biology, and most of genetics —
4968-433: The adenines of one strand are paired with the thymines of the other strand, and so on. Due to the chemical composition of the pentose residues of the bases, DNA strands have directionality. One end of a DNA polymer contains an exposed hydroxyl group on the deoxyribose ; this is known as the 3' end of the molecule. The other end contains an exposed phosphate group; this is the 5' end . The two strands of
5060-435: The cell. Paracellular permeability depends on transport through the spaces that exist between epithelial cells. It is regulated by cellular junctions that are localized in the laminal membranes of the cells. This is the main route of passive flow of water and solutes across the intestinal epithelium. Regulation depends on the intercellular tight junctions which have the most influence on paracellular transport. Studies using
5152-436: The combined influence of polygenes (a set of different genes) and gene–environment interactions . Some genetic traits are instantly visible, such as eye color or the number of limbs, others are not, such as blood type , the risk for specific diseases, or the thousands of basic biochemical processes that constitute life . A gene can acquire mutations in its sequence , leading to different variants, known as alleles , in
5244-402: The complexity of these diverse phenomena, where a gene is defined as a union of genomic sequences encoding a coherent set of potentially overlapping functional products. This definition categorizes genes by their functional products (proteins or RNA) rather than their specific DNA loci, with regulatory elements classified as gene-associated regions. The existence of discrete inheritable units
5336-545: The development of IBD. Detrimental changes in the intestinal microbiota induce an inappropriate (uncontrolled) immune response that results in damage to the intestinal epithelium. Breaches in this critical barrier (the intestinal epithelium) allow further infiltration of microbiota that, in turn, elicit further immune responses. IBD is a multifactorial disease that is nonetheless driven in part by an exaggerated immune response to gut microbiota that causes defects in epithelial barrier function. Bile acids are normal components of
5428-457: The digestive tract, the distribution of the different types of epithelial cells varies according to the function of that region. Important for the barrier function of intestinal epithelium, its cells are joined securely together by four types of cell junction which can be identified at the ultrastructural level: Gap junctions bring the adjacent cells within 2 nanometers of each other. They are formed by several homologous proteins encoded by
5520-550: The dimerization domain, which forms a four-helix bundle where two α helices are separated by a turn; the DNA-binding motif, which forms a helix-turn-helix structure; and the POU-homeodomain, which is composed of three α helices, contained in the motif. This homeodomain is considered atypical due to an extended loop inserted between the second and third helices relative to the canonical homeodomain fold. The atypical insertion
5612-524: The distinction between a heterozygote and homozygote , and the phenomenon of discontinuous inheritance. Prior to Mendel's work, the dominant theory of heredity was one of blending inheritance , which suggested that each parent contributed fluids to the fertilization process and that the traits of the parents blended and mixed to produce the offspring. Charles Darwin developed a theory of inheritance he termed pangenesis , from Greek pan ("all, whole") and genesis ("birth") / genos ("origin"). Darwin used
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#17330860502375704-410: The early 1950s the prevailing view was that the genes in a chromosome acted like discrete entities arranged like beads on a string. The experiments of Benzer using mutants defective in the rII region of bacteriophage T4 (1955–1959) showed that individual genes have a simple linear structure and are likely to be equivalent to a linear section of DNA. Collectively, this body of research established
5796-404: The electron microscope showed that the electrical resistance of epithelial layers depends on the complexity and number of filaments within the tight junction transmembrane protein complexes. Also, the plasma membrane resistance and variable transmembrane conductance of the epithelial cells can also modulate paracellular pathway function. The barrier formed by the intestinal epithelium separates
5888-410: The epithelial layer. To securely contain the contents of the intestinal lumen , the cells of the epithelial layer are joined together by tight junctions , thus forming a contiguous and relatively impermeable membrane. Epithelial cells are continuously renewed every 4–5 days through a process of cell division, maturation, and migration. Renewal relies on proliferative cells ( stem cells ) that reside at
5980-425: The expression of acute phase proteins , such as fibrinogen , c-reactive protein , and interleukin 1 receptor , which are involved with inflammation. Moreover, significantly lower levels of HNF-1α in pancreatic tumors and hepatocellular adenomas than in normal adjacent tissues was observed, suggesting that HNF-1α might play a possible tumor suppressor role. HNF1A mutations can cause maturity onset diabetes of
6072-454: The external environment (the contents of the intestinal lumen ) from the body and is the most extensive and important mucosal surface of body. The intestinal epithelium serves several crucial functions, exhibiting both innate and adaptive immune features. It closely monitors its intracellular and extracellular environment, communicates messages to neighbouring cells and rapidly initiates active defensive and repair measures, if necessary. On
6164-514: The fact that both protein-coding genes and noncoding genes have been known for more than 50 years, there are still a number of textbooks, websites, and scientific publications that define a gene as a DNA sequence that specifies a protein. In other words, the definition is restricted to protein-coding genes. Here is an example from a recent article in American Scientist. ... to truly assess the potential significance of de novo genes, we relied on
6256-487: The final digestive stages of luminal carbohydrates and proteins. The monosaccharides and amino acids thus produced are subsequently transported across the intestinal epithelium and eventually into the bloodstream. The absorption of electrolytes and water is one of the most important functions of the digestive tract. Water absorption is passive and isotonic - depending on the speed and direction of solute flow. Other factors influencing fluid absorption are osmolarity and
6348-413: The functional product. The discovery of introns in the 1970s meant that many eukaryotic genes were much larger than the size of the functional product would imply. Typical mammalian protein-coding genes, for example, are about 62,000 base pairs in length (transcribed region) and since there are about 20,000 of them they occupy about 35–40% of the mammalian genome (including the human genome). In spite of
6440-630: The gene that is described in terms of DNA sequence. There are many different definitions of this gene — some of which are misleading or incorrect. Very early work in the field that became molecular genetics suggested the concept that one gene makes one protein (originally 'one gene - one enzyme'). However, genes that produce repressor RNAs were proposed in the 1950s and by the 1960s, textbooks were using molecular gene definitions that included those that specified functional RNA molecules such as ribosomal RNA and tRNA (noncoding genes) as well as protein-coding genes. This idea of two kinds of genes
6532-477: The genetic predisposition of the individual, the development of inflammation , infection , allergies , autoimmune diseases or cancer - within the intestine itself or other organs. Although they primarily function as part of the digestive system , enterocytes of the intestinal epithelium also express toll-like receptors and nucleotide oligomerization domain proteins that recognize diverse types of microbes and contribute to immune system function. Thus
6624-421: The genome. The vast majority of organisms encode their genes in long strands of DNA (deoxyribonucleic acid). DNA consists of a chain made from four types of nucleotide subunits, each composed of: a five-carbon sugar ( 2-deoxyribose ), a phosphate group, and one of the four bases adenine , cytosine , guanine , and thymine . Two chains of DNA twist around each other to form a DNA double helix with
6716-421: The genomes of complex multicellular organisms , including humans, contain an absolute majority of DNA without an identified function. This DNA has often been referred to as " junk DNA ". However, more recent analyses suggest that, although protein-coding DNA makes up barely 2% of the human genome , about 80% of the bases in the genome may be expressed, so the term "junk DNA" may be a misnomer. The structure of
6808-428: The intestinal epithelium not only serves as a physical barrier separating the intestinal lumen from the body proper but also carries out pathogen recognition functions as part of the intrinsic immune system . Loss of integrity of the intestinal epithelium plays a key pathogenic role in inflammatory bowel disease (IBD). Changes in the composition of the intestinal microbiota are an important environmental factor in
6900-425: The intestinal epithelium. On the other hand, various diseases and conditions can lead to its dysfunction which, in turn, can lead to further complications. The intestinal epithelium is part of the mucosal lining. The epithelium is simple cuboidal epithelium composed of a single layer of cells, while the other two layers of the mucosa, the lamina propria and the muscularis mucosae , support and communicate with
6992-501: The intracellular domains of tight junctions interact with different scaffold proteins , adapter proteins and signaling complexes to regulate cytoskeletal linking, cell polarity, cell signaling and vesical trafficking. Tight junctions provide a narrow but modifiable seal between adjacent cells in the epithelial layer and thereby provide selective paracellular transport of solutes. While previously thought to be static structures, tight junctions are now known to be dynamic and can change
7084-489: The management of type II diabetes including dipeptidyl peptidase-IV (DPP-IV/CD26). HNF-1α is also involved in various metabolic pathways of other organs, such as being a transcriptional regulator of bile acid transporters in the intestine and kidneys. HNF-1α is involved in the promotion of hepatic organic cation transporters , which uptake certain classes of pharmaceuticals ; hence, the loss of its function can lead to drug metabolism problems. In addition, HNF-1α regulates
7176-413: The nucleus. Splicing, followed by CPA, generate the final mature mRNA , which encodes the protein or RNA product. Many noncoding genes in eukaryotes have different transcription termination mechanisms and they do not have poly(A) tails. Many prokaryotic genes are organized into operons , with multiple protein-coding sequences that are transcribed as a unit. The genes in an operon are transcribed as
7268-490: The one hand, it acts as a barrier, preventing the entry of harmful substances such as foreign antigens , toxins and microorganisms . On the other hand, it acts as a selective filter which facilitates the uptake of dietary nutrients , electrolytes , water and various other beneficial substances from the intestinal lumen. When barrier integrity is lost, intestinal permeability increases and uncontrolled passage of harmful substances can occur. This can lead to, depending on
7360-431: The phosphate–sugar backbone spiralling around the outside, and the bases pointing inward with adenine base pairing to thymine and guanine to cytosine. The specificity of base pairing occurs because adenine and thymine align to form two hydrogen bonds , whereas cytosine and guanine form three hydrogen bonds. The two strands in a double helix must, therefore, be complementary , with their sequence of bases matching such that
7452-447: The relevance of HNF1A in diabetes patients and how pharmacogenetics can contribute in patient care. For example, patients with maturity onset diabetes of the young owing to mutations in HNF1A (which accounts for ~3% of all diabetes mellitus cases diagnosed under the age of 30 years) are extremely sensitive to sulfonylurea treatment and can successfully transition off insulin treatment. Likewise, patients with diabetes caused by mutations in
7544-490: The size of the opening between cells and thereby adapt to the different states of development, physiologies and pathologies. They function as a selective and semipermeable paracellular barrier between apical and basolateral compartments of the epithelial layer. They function to facilitate the passage of small ions and water-soluble solutes through the paracellular space while preventing the passage of luminal antigens, microorganisms and their toxins. The intestinal epithelium has
7636-451: The specific intestinal region. Regulated selective permeability is performed through two major routes: the transcellular (transepithelial) route and the paracellular route. This consists of specific transport of solutes across the epithelial cells. It is predominantly regulated by the activities of specialised transporters that translocate specific electrolytes, amino acids, sugars, short chain fatty acids and other molecules into or out of
7728-467: The strand of DNA like a train on a monorail, transcribing it into its messenger RNA form. This point brings us to our second important criterion: A true gene is one that is both transcribed and translated. That is, a true gene is first used as a template to make transient messenger RNA, which is then translated into a protein. This restricted definition is so common that it has spawned many recent articles that criticize this "standard definition" and call for
7820-461: The sugar ribose rather than deoxyribose . RNA also contains the base uracil in place of thymine . RNA molecules are less stable than DNA and are typically single-stranded. Genes that encode proteins are composed of a series of three- nucleotide sequences called codons , which serve as the "words" in the genetic "language". The genetic code specifies the correspondence during protein translation between codons and amino acids . The genetic code
7912-474: The surface and crypt cells can perform both secretory and absorptive functions and that, in fact, these functions can occur simultaneously. Overlaying the brush border of the apical surface of the enterocytes is the glycocalyx , which is a loose network composed of the oligosaccharide side chains of integral membrane hydrolases and other enzymes essential for the digestion of proteins and carbohydrates. These glycoproteins , glycolipids , and enzymes catalyze
8004-805: The term gemmule to describe hypothetical particles that would mix during reproduction. Mendel's work went largely unnoticed after its first publication in 1866, but was rediscovered in the late 19th century by Hugo de Vries , Carl Correns , and Erich von Tschermak , who (claimed to have) reached similar conclusions in their own research. Specifically, in 1889, Hugo de Vries published his book Intracellular Pangenesis , in which he postulated that different characters have individual hereditary carriers and that inheritance of specific traits in organisms comes in particles. De Vries called these units "pangenes" ( Pangens in German), after Darwin's 1868 pangenesis theory. Twenty years later, in 1909, Wilhelm Johannsen introduced
8096-436: The term gene , he explained his results in terms of discrete inherited units that give rise to observable physical characteristics. This description prefigured Wilhelm Johannsen 's distinction between genotype (the genetic material of an organism) and phenotype (the observable traits of that organism). Mendel was also the first to demonstrate independent assortment , the distinction between dominant and recessive traits,
8188-412: The term "gene" (inspired by the ancient Greek : γόνος, gonos , meaning offspring and procreation) and, in 1906, William Bateson , that of " genetics " while Eduard Strasburger , among others, still used the term "pangene" for the fundamental physical and functional unit of heredity. Advances in understanding genes and inheritance continued throughout the 20th century. Deoxyribonucleic acid (DNA)
8280-414: The young type 3 , one of the forms of " monogenic diabetes ", as well as hepatocellular adenoma . HNF-1 protein is present in ovarian clear-cell carcinoma . In humans, mutations in HNF1A cause diabetes that responds to low dose sulfonylurea agents. The identification of extreme sulfonylurea sensitivity in patients with diabetes mellitus owing to heterozygous mutations in HNF1A presents a clear example of
8372-446: Was first suggested by Gregor Mendel (1822–1884). From 1857 to 1864, in Brno , Austrian Empire (today's Czech Republic), he studied inheritance patterns in 8000 common edible pea plants , tracking distinct traits from parent to offspring. He described these mathematically as 2 combinations where n is the number of differing characteristics in the original peas. Although he did not use
8464-430: Was shown to be the molecular repository of genetic information by experiments in the 1940s to 1950s. The structure of DNA was studied by Rosalind Franklin and Maurice Wilkins using X-ray crystallography , which led James D. Watson and Francis Crick to publish a model of the double-stranded DNA molecule whose paired nucleotide bases indicated a compelling hypothesis for the mechanism of genetic replication. In
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