Haplotype is a set of single nucleotide polymorphisms (SNPs) on a single chromatid that are statistically associated. It is thought that these associations, and the identification of a few alleles of a haplotype block, can unambiguously identify all other polymorphic sites in its region. Such information is very valuable for investigating the genetics behind common diseases, and is collected by the International HapMap Project.
An organism's genotype may not uniquely define its haplotype. For example, consider a diploid organism and two bi-allelic loci on the same chromosome such as Single Nucleotide Polymorphisms (SNPs). The first locus has alleles A and T with three possible genotypes AA, AT, and TT, the second locus having G and C, again giving three possible genotypes GG, GC, and CC. For a given individual, there are therefore nine possible configurations for the genotypes at these two loci, as shown in the punnett square , which shows the possible genotypes that an individual may carry and the corresponding haplotypes that these resolve to. For individuals that are homozygous at one or both loci, it is clear what the haplotypes are; it is only when an individual is heterozygous at both loci that the phase is ambiguous.
Within the human genome SNPs occur on an average of 1 in 1000 base pairs .researchers have shown the groups of SNPs occur in predictable patterns within sections of DNA.
these inherent sections of 68 SNPs are called haplotype.Within one section of DNA it is believed that there are only 3 to 5 different haplotypes throughout the entire population.
The only unequivocal method of resolving phase ambiguity is by sequencing. However, it is possible to estimate the probability of a particular haplotype when phase is ambiguous using a sample of individuals.
Chk out this video: http://www.youtube.com/watch?v=oLz-II0eZvk
Given the genotypes for a number of individuals, the haplotypes can be inferred by haplotype resolution or haplotype phasing techniques. These methods work by applying the observation that certain haplotypes are common in certain genomic regions. Therefore, given a set of possible haplotype resolutions, these methods choose those that use fewer different haplotypes overall. The specifics of these methods vary - some are based on combinatorial approaches (e.g., parsimony), whereas others use likelihood functions based on different models and assumptions such as the Hardy-Weinberg principle, the coalescent theory model, or perfect phylogeny. These models are combined with optimization algorithms such as expectation-maximization algorithm (EM) or Markov chain Monte Carlo (MCMC).
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Showing posts with label chromosome 2. Show all posts
Showing posts with label chromosome 2. Show all posts
Wednesday, December 17, 2008
Tuesday, December 16, 2008
Evolutionary significance of Human Chromosome 2
All apes apart from man have 24 pairs of chromosomes. There is therefore a hypothesis that the common ancestor of all great apes had 24 pairs of chromosomes and that the fusion of two of the ancestor's chromosomes created chromosome 2 in humans. The evidence for this hypothesis is very strong.
The Evidence
Evidence for fusing of two ancestral chromosomes to create human chromosome 2 and where there has been no fusion in other Great Apes is:
1) The analogous chromosomes (2p and 2q) in the non-human great apes can be shown, when laid end to end, to create an identical banding structure to the human chromosome 2.
2) The remains of the sequence that the chromosome has on its ends (the telomere) is found in the middle of human chromosome 2 where the ancestral chromosomes fused.
3) the detail of this region (pre-telomeric sequence, telomeric sequence, reversed telomeric sequence, pre-telomeric sequence) is exactly what we would expect from a fusion.
4) this telomeric region is exactly where one would expect to find it if a fusion had occurred in the middle of human chromosome 2.
5) the centromere of human chromosome 2 lines up with the chimp chromosome 2p chromosomal centromere.
6) At the place where we would expect it on the human chromosome we find the remnants of the chimp 2q centromere .
Not only is this strong evidence for a fusion event, but it is also strong evidence for common ancestry; in fact, it is hard to explain by any other mechanism.
Centromere evidence
Let us re-iterate what we find on human chromosome 2. Its centromere is at the same place as the chimpanzee chromosome 2p as determined by sequence similarity. Even more telling is the fact that on the 2q arm of the human chromosome 2 is the unmistakable remains of the original chromosome centromere of the common ancestor of human and chimp 2q chromosome, at the same position as the chimp 2q centromere (this structure in humans no longer acts as a centromere for chromosome 2.
Refered
http://www.evolutionpages.com/chromosome_2.htm
Hope You Like This Post, Let me know what you feel about this blog.
Email me : help.me.ishan@gmail.com
The Evidence
Evidence for fusing of two ancestral chromosomes to create human chromosome 2 and where there has been no fusion in other Great Apes is:
1) The analogous chromosomes (2p and 2q) in the non-human great apes can be shown, when laid end to end, to create an identical banding structure to the human chromosome 2.
2) The remains of the sequence that the chromosome has on its ends (the telomere) is found in the middle of human chromosome 2 where the ancestral chromosomes fused.
3) the detail of this region (pre-telomeric sequence, telomeric sequence, reversed telomeric sequence, pre-telomeric sequence) is exactly what we would expect from a fusion.
4) this telomeric region is exactly where one would expect to find it if a fusion had occurred in the middle of human chromosome 2.
5) the centromere of human chromosome 2 lines up with the chimp chromosome 2p chromosomal centromere.
6) At the place where we would expect it on the human chromosome we find the remnants of the chimp 2q centromere .
Not only is this strong evidence for a fusion event, but it is also strong evidence for common ancestry; in fact, it is hard to explain by any other mechanism.
Centromere evidence
Let us re-iterate what we find on human chromosome 2. Its centromere is at the same place as the chimpanzee chromosome 2p as determined by sequence similarity. Even more telling is the fact that on the 2q arm of the human chromosome 2 is the unmistakable remains of the original chromosome centromere of the common ancestor of human and chimp 2q chromosome, at the same position as the chimp 2q centromere (this structure in humans no longer acts as a centromere for chromosome 2.
Refered
http://www.evolutionpages.com/chromosome_2.htm
Hope You Like This Post, Let me know what you feel about this blog.
Email me : help.me.ishan@gmail.com
Monday, December 15, 2008
ALS2 Gene
The official name of ALS2 gene is amyotrophic lateral sclerosis 2 (juvenile)..The ALS2 gene provides instructions for making a protein called alsin. Alsin is produced in a wide range of tissues, with highest amounts in the brain. It is particularly abundant in motor neurons, the specialized nerve cells in the brain and spinal cord that control the movement of muscles.
Alsin's function in cells is unclear. It may play a role in regulating cell membrane organization and the movement of molecules inside cells. Research findings also suggest that alsin may play a role in the development of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses.
Location:
ALS2 gene is present in human chromosome 2 and ts coded from region 202,273,521 to 202,353,982 with 34 exons, the cytogenetic location 2q33.2
Disease
Mutation in the ALS2 Gene causes Amyotrophic lateral Sclerosis(ALS),infantile-onset ascending hereditary spastic paralysis ,juvenile primary lateral sclerosis.In all three disease mutations delete a single DNA building block (nucleotide), which alters the instructions for producing alsin. As a result, alsin is unstable and decays rapidly.
Alsin's function in cells is unclear. It may play a role in regulating cell membrane organization and the movement of molecules inside cells. Research findings also suggest that alsin may play a role in the development of axons and dendrites, which are specialized outgrowths from nerve cells that are essential for the transmission of nerve impulses.
Location:
ALS2 gene is present in human chromosome 2 and ts coded from region 202,273,521 to 202,353,982 with 34 exons, the cytogenetic location 2q33.2
Disease
Mutation in the ALS2 Gene causes Amyotrophic lateral Sclerosis(ALS),infantile-onset ascending hereditary spastic paralysis ,juvenile primary lateral sclerosis.In all three disease mutations delete a single DNA building block (nucleotide), which alters the instructions for producing alsin. As a result, alsin is unstable and decays rapidly.
COL4A3 Gene
The official name of COL4A3 gene is collagen, type IV, alpha 3 (Goodpasture antigen). COL4A3 gene provides instructions for making one component of type IV collagen. which is a flexible protein that forms complex networks. Specifically, this gene makes the alpha3(IV) chain of type IV collagen. This chain combines with two other types of alpha (IV) chains (the alpha4 and alpha5 chains) to make a complete collagen molecule. Type IV collagen networks make up a large portion of basement membranes, which are thin sheet-like structures that separate and support cells in many tissues. This specific type IV collagen network plays an especially important role in the basement membranes of the kidney, inner ear, and eye.
Function:
Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3.In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein.
COL4A3 gene is present in human chromosome 2 and its coded from region 227,737,524 to base pair 227,887,750 with 52 exons, the cytogenetic location 2q36-q37
Disease
Mutations in this gene causes Alport syndrome,The autosomal recessive form of Alport syndrome results when two copies of the COL4A3 gene in each cell are mutated. Most of the mutations identified in this gene cause a change in the sequence of amino acids (the building blocks of proteins) in a region of the alpha3(IV) collagen chain that is critical for combining with other type IV collagen chains. Other mutations severely decrease or prevent the production of any alpha3(IV) chains in the basement membranes of the kidney, inner ear and eye. In the kidney, other types of collagen accumulate in the basement membranes, eventually leading to scarring of the kidneys and kidney failure. Mutations in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss.
Function:
Type IV collagen, the major structural component of basement membranes, is a multimeric protein composed of 3 alpha subunits. These subunits are encoded by 6 different genes, alpha 1 through alpha 6, each of which can form a triple helix structure with 2 other subunits to form type IV collagen. This gene encodes alpha 3.In the Goodpasture syndrome, autoantibodies bind to the collagen molecules in the basement membranes of alveoli and glomeruli. The epitopes that elicit these autoantibodies are localized largely to the non-collagenous C-terminal domain of the protein.
COL4A3 gene is present in human chromosome 2 and its coded from region 227,737,524 to base pair 227,887,750 with 52 exons, the cytogenetic location 2q36-q37
Disease
Mutations in this gene causes Alport syndrome,The autosomal recessive form of Alport syndrome results when two copies of the COL4A3 gene in each cell are mutated. Most of the mutations identified in this gene cause a change in the sequence of amino acids (the building blocks of proteins) in a region of the alpha3(IV) collagen chain that is critical for combining with other type IV collagen chains. Other mutations severely decrease or prevent the production of any alpha3(IV) chains in the basement membranes of the kidney, inner ear and eye. In the kidney, other types of collagen accumulate in the basement membranes, eventually leading to scarring of the kidneys and kidney failure. Mutations in this gene can also lead to abnormal function in the inner ear, resulting in hearing loss.
Saturday, December 13, 2008
Haplotypes Animation
Haplotype is a set of single nucleotide polymorphisms (SNPs) on a single chromatid that are statistically associated. It is thought that these associations, and the identification of a few alleles of a haplotype block, can unambiguously identify all other polymorphic sites in its region. Such information is very valuable for investigating the genetics behind common diseases, and is collected by the International HapMap Project.
An organism's genotype may not uniquely define its haplotype. For example, consider a diploid organism and two bi-allelic loci on the same chromosome such as Single Nucleotide Polymorphisms (SNPs). The first locus has alleles A and T with three possible genotypes AA, AT, and TT, the second locus having G and C, again giving three possible genotypes GG, GC, and CC. For a given individual, there are therefore nine possible configurations for the genotypes at these two loci, as shown in the punnett square , which shows the possible genotypes that an individual may carry and the corresponding haplotypes that these resolve to. For individuals that are homozygous at one or both loci, it is clear what the haplotypes are; it is only when an individual is heterozygous at both loci that the phase is ambiguous.
Within the human genome SNPs occur on an average of 1 in 1000 base pairs .researchers have shown the groups of SNPs occur in predictable patterns within sections of DNA.
these inherent sections of 68 SNPs are called haplotype.Within one section of DNA it is believed that there are only 3 to 5 different haplotypes throughout the entire population.
The only unequivocal method of resolving phase ambiguity is by sequencing. However, it is possible to estimate the probability of a particular haplotype when phase is ambiguous using a sample of individuals.
Given the genotypes for a number of individuals, the haplotypes can be inferred by haplotype resolution or haplotype phasing techniques. These methods work by applying the observation that certain haplotypes are common in certain genomic regions. Therefore, given a set of possible haplotype resolutions, these methods choose those that use fewer different haplotypes overall. The specifics of these methods vary - some are based on combinatorial approaches (e.g., parsimony), whereas others use likelihood functions based on different models and assumptions such as the Hardy-Weinberg principle, the coalescent theory model, or perfect phylogeny. These models are combined with optimization algorithms such as expectation-maximization algorithm (EM) or Markov chain Monte Carlo (MCMC)
An organism's genotype may not uniquely define its haplotype. For example, consider a diploid organism and two bi-allelic loci on the same chromosome such as Single Nucleotide Polymorphisms (SNPs). The first locus has alleles A and T with three possible genotypes AA, AT, and TT, the second locus having G and C, again giving three possible genotypes GG, GC, and CC. For a given individual, there are therefore nine possible configurations for the genotypes at these two loci, as shown in the punnett square , which shows the possible genotypes that an individual may carry and the corresponding haplotypes that these resolve to. For individuals that are homozygous at one or both loci, it is clear what the haplotypes are; it is only when an individual is heterozygous at both loci that the phase is ambiguous.
Within the human genome SNPs occur on an average of 1 in 1000 base pairs .researchers have shown the groups of SNPs occur in predictable patterns within sections of DNA.
these inherent sections of 68 SNPs are called haplotype.Within one section of DNA it is believed that there are only 3 to 5 different haplotypes throughout the entire population.
The only unequivocal method of resolving phase ambiguity is by sequencing. However, it is possible to estimate the probability of a particular haplotype when phase is ambiguous using a sample of individuals.
Given the genotypes for a number of individuals, the haplotypes can be inferred by haplotype resolution or haplotype phasing techniques. These methods work by applying the observation that certain haplotypes are common in certain genomic regions. Therefore, given a set of possible haplotype resolutions, these methods choose those that use fewer different haplotypes overall. The specifics of these methods vary - some are based on combinatorial approaches (e.g., parsimony), whereas others use likelihood functions based on different models and assumptions such as the Hardy-Weinberg principle, the coalescent theory model, or perfect phylogeny. These models are combined with optimization algorithms such as expectation-maximization algorithm (EM) or Markov chain Monte Carlo (MCMC)
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