What is a T allele in human genetics?

Question

I am researching genetic predisposition to usefulness of some anti-depressants against others. Many reports suggest the T allele of G protein B3 is associated with a response. What is the T allele?

Answer 1

allele A variant form of a gene. In a diploid cell there are two alleles of every gene (one inherited from each parent, although they could be identical). Within a population there may be many alleles of a gene. Alleles are symbolized with a capital letter to denote dominance, and lower case for recessive. In heterozygotes with co-dominant alleles, both are expressed.

I dont know what T alleles are in Humans..But will look it up

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The T gene in mammals





Abstract


Brachyury or the T-gene plays a significant role for differentiation and development of the notochord and mesoderm during the early embryology of vertebrates. T belongs to a unique family of genes, characterised by the T-box, a special sequens that encodes DNA binding proteins. T-box genes exist in several different animals, from the `simple´ Hydra to Homo sapiens. A common function of the T-box is regulation of transcription and perhaps for that reasons does they show conservatism in both t-box sequence and target as well as a function that seems related.

Mammalian embryos heterozygous for the T mutation is not capable of complete their axial development and is therefore born with a bobtail. Homozygotes show severe defects in the posterior end and die due to lack of circulation between embryo and the mother. The phenotypic effect of this mutation is properly cause by alternations of cell adhesion abilities blocking the normal migration of cells though the primitive streak and thereby hamper elongation of the craniocaudale axis and development of mesoderm structures.





Embryonic development of mesoderm and chorda


Far the most of the more `advanced´ organisms are grouped together as bilateral organisms, meaning organism that are characterised by two tings: They are developed around to axis, the anteroposterior axis (rear and hind) and the dorsoventrale (up and down) and they are triploblastisc which means they consist of three germ layer: ectoderm, endoderm and mesoderm. All types of tissues in a fully developed organism, originate from these three germ layers. Ectoderm is differentiated into epidermis (skin) and neurone structures, endoderm to gut and mesoderm is the precursor to muscles, connective tissue, cartilage and bones. More `primitive´ organisms like the medusa consist of only one axis and is furthermore diploblastisc, meaning composted of only to germ layers; the ectoderm and the endoderm.

The evolutionary transition from diploblastisc to triploblastisc does by that imply development of both more than one axis and generation of mesoderm. Both characters are present at the same time in all triploblastisc, indicating that the development of these fundamentally changes has occurred at the same evolutionary time. Embryonic development of axis and mesoderm has for that reason to be two quite essential events in the formation of bilateral embryos.

A vertebrate in the early blastula stage (very early in the embryonic stage, the embryo consist of only a small ball of cells) is composted of two layers, the epiblast from which all the embryos future structures are form and an outer visceral endoderm. At this time only the precursor of one of the axis will exist, the vegetative pole and the animal pole (respectively the yolk containing part of the eggcell where dividing are fast, and the part of the eggcell with out yolk where dividing is slower). Generation of the primitive streak is the first indication of development of the other axis, the anteroposterior axis. It consist of a thicken edge of cells and is generated from the embryonic blastodisc. The source of the primitive streak does at the same time indicate the posterior end of the embryo.

The future mesoderm is form by vegetale cells migration from the epiblast via the primitive streak to the space between the original two layers. Here they will take position along the embryos axis (paraxial position) and will eventually generate the basis of the epithelial somit. Somit consist of segmented units of mesoderm cells and it is them that form the precursor of the embryos muscles, bones and cartilage. The mesoderm-inducing signal is thought to be release from future ectoderm cells. Such signals is present already at cell stage 32, when yet no transcription is taking place. The explanation to this is that these signals are present in the vegetale cytoplasm at oogenese (generation of the egg cell), either as maternal mRNA (coming from the mother) or as a protein encoding secreting factors. Maternal signals though, are not nearly as strong as later transcripts that are initiated when the blastula reach the mitt blastula stage at around 4000 cells.

Induction of mesoderm is of great important for the triploblastisc organisms. The vast part of the grown animals body is made up by mesoderm and the mesoderm has a significant role in prolongation of the embryo, development of posterior parts like the tail, and also differentiation of other tissues.

Development of the notochord (string-like structure which function originate has been strengthen, is later replaced by the spinal cord) plays a significant role in later organisation and differentiation of the axial structures in the embryo. The precursor of the notochord is like the mesoderm based on cells from the epiblast. These cells gather at a single point in the tip of the primitive streak and forms a special structure know as the node, from which further accumulation of cells leads to formation of the notochord. In mice these precursors cells is formed immediate before generation of the first somits and by the 6. somit stage the notochord it fully developed and stretch in the length of the embryo, still yet connected to dorsale wall of the gut and neurone cord though. By somit stage 25 does the notochord separate from the gut and neurone cord.

Some intensive research concerning embryonic and evolutionary development of the mesoderm and notochord has been going on. The evolutionary development of the mesoderm is somewhat of a mystery. The general believe though, is that the original function can be traced back by comparing the expression pattern and function in `more primitive´ animals in possessions of genes showing homology. The embryonic development of mesoderm is a complicated process in which research has identified several separate loci involved. Brachyury or the T-gene is believed to be off great importance for the formation of the tail in vertebrates (with special focus on mammals).





Brachyury


Brachyury belongs to a very special group of genes that are characterised by containing a highly conservative sequence called a T-box. This sequence has proved to exist in a long line of organism, not only vertebrate but also other triploblastisc and even some diploblastisc animals. The function has been proved to highly conservative as well, like Brachyury from fish can activate target genes in amphibians.

The T-box genes have a quite special function encoding proteins that binds specific to a small DNA target sequence. Such proteins are called DNA binding proteins and functions as either repressor or activators of expression, meaning that the function is not directly expression of a gene product, but more indirectly by impede or increase another gene product.

A lot of the T-box genes are involved in development of the embryo and Brachyury is no exception. Both molecular and embryonic data suggested that Brachyury is involved in regulation of gene transcription needed for generation and differentiation of mesoderm and function of the notochord. The function is believed to be activation of such genes, meaning that it increase the expression of these genes gene product. An increased need for functional T protein can therefore be observed along the anteriorposterier axis in young embryos.

The gene product of the T-boks genes, the T-protein, consisted amongst others of a highly conservative sequence of around 200 amino acids called the T domain. This domain is positioned in the N-terminal of the protein and is responsible for the DNA binding properties. The target sequence for the T protein, meaning the DNA sequence that T protein binds, is found to be a small, almost palindromic sequence of around 20 base pairs T(G/C)CACCTAGGTGTGAAATT.

The C terminal has been observed to be of a higher degree of variation, but experience with truncated proteins (deletion of part of the coding sequence) in mice has show indication of a profound function. DNA binding is apparently not hammed in these mutated proteins meaning that the N-terminal must be intact, indicating that deletion must have occurred in the C-terminal. The C-terminal is by that responsible for activation of transcription in T proteins.

The unique bobtailed phenotype (Brachyury phenotype) is cause by a deletion of about 200 kilo bases, which corresponded to the entire coding part of the T gene, meaning both N- and C-terminal. Individuals that are heterozygous for this mutation are not capable of completing development of the axis and are therefore born with a bobtail. Homozygous on the other hand are not capable of generate the posterior end and dies in the middle of the embryonic stage.

Early experimental crossing with amongst others mice has shown that breeding between bobtailed individuals and individuals with normal tail will results in offspring in the ratio of one bobtail to one normal tail. Crossing between two bobtailed mice however resulted in offspring in the ratio two bobtailed : one normal tail. Mice that were pure-breeding in regards to bobtail, was not observed. The conclusion was that the bobtailed phenotype was caused by a single dominant factor, transmitted in a simple Mendel fashion and that the homozygote is lethal. The varied length of tails was believed to be due to interactions with modifier genes. Later experiments with dissection, like mentioned below, did however show that Brachyury displays a special dominance relationship called incomplete dominance. In this kind of transmission the heterozygous phenotype will appear as the intermediary between the two homozygous characters. Brachyury is furthermore a pleiotropic gene which means a gene that control several, apparently unrelated phenotypic characters.By dissecting of the uterus in different stages after copulation (mating), the scientists discovered that the homozygous embryos died shortly after day 10 after copulation and where reabsorb by the mother. Another thing they discovered was that the homozygous suffered from severe morphologic changes: development of the posterior axial was highly defective, especially did the lack of functionally T gene influence the generation of the primitive streak, precursors of the notochord and chorda-mesoderm. These areas correspond to those areas that in the wildtype is characterised by the highest T expression.

This dissection of the mice embryos revealed a fairly detailed description of the homozygote development. Till day number 8 after copulation no morphologic sign of homozygotism worth mention existed, after that however it was pretty easy to recognize them from the wildtype and heterozygous embryos. First, the numbers of somits were lesser than normal and those somits present were often irregular and not fully developed. By day 10 the wildtype embryo had generated up till 30 somits like frontleg buds clearly were visible and hind leg buds has just starting to develop. The homozygote embryos on the other hand were highly reduced in the posterior end, both accordingly to tail and hind leg buds furthermore did the mitt-dorsal line and the front legs showe sign of abnormality. Some differentiation of notochord could apparently take place in an early stage, but never as regular as in embryos of the wildtype. Shortly before day 10 after copulation however all signs of such a structure would disappeared and around the time of death no evident of a notochord ever being present was found.

Irregularities of the nervous system could furthermore be observed in homozygous embryos. The neurones where asymmetrically and was sending out more branches than normal which in addition were larger than the neurones themselves. Generation of dorsale ganglia did neither seem to take place. As generation of notochord plays an important role for the development of the nervous system too, could it be that the insufficient development of the notochord could be caused by lack of ganglia and abnormalities in the nervous system. The vascular system seems to be affected in the homozygote as well. Heart and vessels did not follow the normal development, several blood-filled sinus and an enlarged pericardial cavity were present in the embryo like a decreased function of the heart could be observed.

These phenotypic changes, severe as they seem, does not cause died of the homozygote embryos, it is more likely that lack of nutrients due to defects in the abilities to generate connection between allantois and placenta, the precursor to the umbilical cord, could cause death. Experiments with dissecting tissue samples of homozygote embryos and grow them in a media in vitro, showed that it actually was possible to keep these samples alive beyond the time of natural death in vivo, indicating that the changes in the tissue isn’t responsible for the embryos death.

Heterozygotes too seem to be showing characteristics different from the wildtype embryos. They were not able to complete the axial development, although not in the same severe degree as the homozygote, and would therefore be born with a tail shorter than normal. Dissection of embryos from different stages just like in the homozygote revealed that the heterozygous embryos too showed abnormality in the posterior end, especially in the lumbar part. The notochord seemed reduced in these regions, nervation was abnormal although never in the same degree as the homozygote, and some time could abnormalities in the sacral vertebra exist. Often could the terminal vertebra at the constriction in the tail be observed as being thinner and smaller.

Experiments indicate that an alternation in the molecular structure of the mesoderm cells surface protein could be an explanation for the mutated phenotype.

By dissecting embryos from the uterus and staining them, did an uneven distribution of the mutant cells seems to exist along the craniocaudale axis; the mutant cells was found to be prevalent in posterior part, especially the tail bud. The reason to this could be that T/T cells in the primitive streak are defect in their ability to migrate from the mitt-line and populate the mesoderm. As a consequence of this the mutant cells would accumulated in the regions responsible for axial prolongation and at the same time also block this. At the same time it turned out that a high contribution of T/T cells caused severe abnormalities, while lesser concentrations caused deformations of tail and allantois only. The cells in these regions seemed to form close clusters, which could indicate that the accumulation of cells perhaps was caused by an increased cell : cell adhesion. The T/T cell did usually not blend in with the wildtype cells, but created thick clusters of mutated tissues instead. Rarely though, T/T cells was observed to integrate as strings of mutated tissue in the notochord. The last could be an explanation why, although very rarely, severely abnormal puppies can be born.

Accumulation of mutated cell could very well be a possible explanation for the defects observed in the heterozygous embryos too. In the same regions where homozygotes accumulate T/T cells, the heterozygotes seem to be in possession of an increased part of T/+ cells. Because of competitive competition in DNA binding between wildtype and heterozygous cells defects in the tail can be observed. An quite odd effect of the T mutation is that although the posterior parts seems to contain an insufficient part of mesodermal cell, the ectodermic part seem to contains to many cells. This will result in an overproduction of skin in this area.

Several alleles of Brachyury are identified today, like Brachyury is found to be under the influence of several other loci. Mention them all will be to comprehensive, only a short description of couple of the most important loci will for that reason be made.

t or tct (the complex tail mutation) is believed to be a haplotype of T, meaning that both are positioned on the same chromosome, near the same locus and are coding for related characters. The odd thing about t is that heterozygous (t/+) or homozygous (t/t) does not show any phenotype different from the wildtype. If t on other hand is expressed with T (T/t) the individual will be born without a tail, instead of a Bobtail; t has no phenotype of its own, but enhances the phenotype expressed by T.

Scientists have also found some proof of the existed of alleles from another loci that completely normalised the mutated T phenotype, meaning that such alleles would abolish the function of T. th7 is such an allele first isolated in mice. Heterozygous (T/ th7) has showed completely to normalise the phenotype. It is properly an unlinked factor from another locus, which function is connected with T, some scientist speculated that it could be copy of the wildtype allele.





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Answer 2

You yourself have inherited genes of both your parents, so there is a gene that expresses itself now as blue but you may have a lighter gene such as a different clearer blue. But no brown. Same for your husband he has the hazel expressing itself, but he may have blue or light Green as his other gene. If his other gene in not cleared then all your children will have hazel eyes. If he does have a lighter gene, and so do you, then you'll have combination of 1 in 4 with each variations. Now it is more complicated than that because the color that expresses is not "set" but happens on a scale like if the gene is green-blue, it can go towards the green or towards the blue. The infinite diversity of the human genome :-) hope that helps. Oh, and yes, brow and blue gives brown...never blue, unless the other gene of the brown eyed person is blue. Explains, how a child can have just the same eyes as a grand parent for example.