Human Genetic Variation
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Human
genomes are to 99.9% identical. The remaining 01.% amounts to about
3 million nucleotides that are different between two individuals. These
differences are what accounts for most of the differences in looks, behavior,
disease susceptibility, drug responses, etc.. |
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The
majority of the differences in the genomes of two humans consist of
single nucleotide polymorphisms or SNPs. SNPs are allelic
positions in the sequences of two genomes that may show an A in one genome
and a T in the other. Or a G in one and an A in the other. Insertions or
deletions are not SNPs. SNPs are nucleotide changes. They occur somewhat
less frequent in regions that are functionally important such as genes and
promoters, than in intergenic regions or introns. On average the genomes
of two individuals contain one SNP per 1,300 nucleotides.
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SNPs can cause mutations. SNPs in
coding regions of genes can lead to different amino acids being placed into the same position into a protein. SNPs in promoters
have the potential to alter gene expression. Even synonymous SNPs in exons (those that do not alter a protein sequence), and
SNPs in introns can cause mutations, e.g. if they disrupt the splicing pattern for a pre-mRNA.
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As
regular features of genome sequences, SNPs are being passed on to offspring.
Since SNPs occur in relative close proximity to each other, groups of SNPs
remain fairly stable and undisturbed by cross overs. Cross overs between
alleles certainly occur and they connect a group of SNPs from one chromosome
to a different group of SNPs from the other. Therefore, groups of SNPs can
be observed that run in different lineages (families and populations) and
are inherited as clusters Such SNP clusters are called "Haplotypes".
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SNPs
are extremely important for medical and biological research. On one
hand, SNPs can cause disease by altering gene regulation, protein function,
etc. On the other hand, SNPs that do not cause alterations may still
be co-inherited with a gene that's involved in disease and could be used
as a marker to signal traits such as risks for disease, drug responsiveness,
etc. Therefore, lots of research efforts are under way to catalogue
human SNPs and to determine those that are in fact correlated with traits
and can be used as indicators in diagnosing and treating disease. |
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The
study of human evolution, population genetics, and migrations benefits
from the availability of SNPs, too. SNPs and haplotypes provide very finely-grained
markers: they are evenly distributed over the human genome and inherited
in groups. An important source for SNP-analysis in humans is mitochondrial
DNA: due to their physicochemical function the mutation rate in mitochondria
is elevated compared to the low mutation rate in the nucleus and more SNPs
are available for study on the comparatively short mitochondrial DNA. Another
advantage of studying SNPs in mitochondria is, that they lend themselves
to the study of single SNPs: mitochondria are passed on from mothers to
their offspring, mitochondria from sperm cells have not been observed in
offspring. Thus, mitochondrial DNA is not subject to the allele shuffling
that occurs during meiosis, and differences in SNP pattern are due to the
occurrence of individual mutations and not to the reshuffling of haplotypes. |
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