2/01/2006
Genetic Variations Implicated In Disease
Sequence differences in less than 0.2% of the 3-billion-base human genome play a vital role in a bewildering variety of human disease. Today, researchers from the Wellcome Trust Sanger Institute and the Cambridge University's Cambridge Institute for Medical Research, together with international colleagues report in PLoS Genetics their detailed maps of differences implicated in disease as well as genes that are unchanged in recent human history.
The Major Histocompatibility Complex (MHC) consists of hundreds of genes on human chromosome 6 that are important in most autoimmune conditions, when our biological defences turn on our own systems.
The MHC has the major role in type 1 diabetes and rheumatoid arthritis. The MHC is also pivotal in response to infection, including malaria and AIDS.
Genes in the MHC can differ dramatically between people, and the differences among us affect medical events as diverse as tissue transplant rejection, arthritis, asthma and disease resistance. A detailed study of this region in different people will shed light on which genes are most important.
"Within the sea of over 20,000 sequence variations across the 4 million MHC bases, we found one island of stability," continued Dr Beck. "A region of 160,000 bases that is up to 200-fold less variant between chromosomes sharing part of the same HLA type, suggesting these individuals most likely shared a common ancestor as recently as 50,000 years ago."
The study further described over 300 amino acid changing variants in gene sequences. These variants are strong candidates for functional studies to understand the role of variation in MHC-associated disease.
Autoimmune disease affects about 3 million people in the UK. The three haplotypes studied here display different susceptibilities to diseases such as type 1 diabetes, myasthenia gravis and multiple sclerosis.
Haplotypes are combinations of gene and sequence variants that tend to occur together in an individual genome. This may be purely fortuitous, or it may reflect selection of given combinations (they have been successful in the past), or it may reflect a population bottleneck, where only a few, perhaps similar, genomes have contributed to the further population growth.
The MHC is among the most gene-dense regions of the human genome and the most variable. Over evolutionary time, the MHC has been driven to become the most variable region of our genome.
The MHC Haplotype Project is studying in fine detail the sequence of eight of the most common human haplotypes, selected for conferring protection against or susceptibility to common disease. The detailed analysis of the third of these eight is reported here and compared with the two previously described.
The COX haplotype has been associated with susceptibility to a wide range of diseases, including type 1 diabetes, systemic lupus erythematosus and myasthenia gravis.
The PGF haplotype provides protection against type 1 diabetes and predisposes to other diseases such as multiple sclerosis and systemic lupus erythematosus.
The QBL haplotype is positively associated with Graves' disease and type 1 diabetes.
ScienceDaily: Researchers Map Of Genetic Variations Implicated In Disease
The Major Histocompatibility Complex (MHC) consists of hundreds of genes on human chromosome 6 that are important in most autoimmune conditions, when our biological defences turn on our own systems.
The MHC has the major role in type 1 diabetes and rheumatoid arthritis. The MHC is also pivotal in response to infection, including malaria and AIDS.
Genes in the MHC can differ dramatically between people, and the differences among us affect medical events as diverse as tissue transplant rejection, arthritis, asthma and disease resistance. A detailed study of this region in different people will shed light on which genes are most important.
"Within the sea of over 20,000 sequence variations across the 4 million MHC bases, we found one island of stability," continued Dr Beck. "A region of 160,000 bases that is up to 200-fold less variant between chromosomes sharing part of the same HLA type, suggesting these individuals most likely shared a common ancestor as recently as 50,000 years ago."
The study further described over 300 amino acid changing variants in gene sequences. These variants are strong candidates for functional studies to understand the role of variation in MHC-associated disease.
Autoimmune disease affects about 3 million people in the UK. The three haplotypes studied here display different susceptibilities to diseases such as type 1 diabetes, myasthenia gravis and multiple sclerosis.
Haplotypes are combinations of gene and sequence variants that tend to occur together in an individual genome. This may be purely fortuitous, or it may reflect selection of given combinations (they have been successful in the past), or it may reflect a population bottleneck, where only a few, perhaps similar, genomes have contributed to the further population growth.
The MHC is among the most gene-dense regions of the human genome and the most variable. Over evolutionary time, the MHC has been driven to become the most variable region of our genome.
The MHC Haplotype Project is studying in fine detail the sequence of eight of the most common human haplotypes, selected for conferring protection against or susceptibility to common disease. The detailed analysis of the third of these eight is reported here and compared with the two previously described.
The COX haplotype has been associated with susceptibility to a wide range of diseases, including type 1 diabetes, systemic lupus erythematosus and myasthenia gravis.
The PGF haplotype provides protection against type 1 diabetes and predisposes to other diseases such as multiple sclerosis and systemic lupus erythematosus.
The QBL haplotype is positively associated with Graves' disease and type 1 diabetes.
ScienceDaily: Researchers Map Of Genetic Variations Implicated In Disease
