|HLA Polymorphism and Disease Association
The major researches of HLA group include three aspects:
HLA polymorphism in Chinese population (allele distribution, population
genetics); SNPs study in HLA classic genes (detection, evolution
mechanism); Complex disease association study (Cerivical cancer,
Ankylosing Spondylitis, IgA nephropathy and Type I diabetes).
1. Anthropology studies in china
Plenty of HLA alleles identified in Chinese populations
suggest a great diversity in Chinese populations.Some of alleles
were detected high frequently in Chinese.Several alleles had clear
south-to-north gradients in their frequencies distribution.Nine
novel alleles were identified, and nomenclatured by WHO.
DQB1 allele frequency distribution in chinese
2.Single Nucleotide Polymorphisms of HLA region in Chinese
We analyze Single Nucleotide Polymorphisms (SNPs) and
haplotypes of HLA classic class I and II genes by using long-fragment
PCR amplification and sequencing. We for the first time analyzed
polymorphisms in the regulatory regions of HLA genes including 5’
promoter and 3’UTR. Moreover, the functional studies suggest
these regions may play an important role in immune regulation. Our
next aim is to construct SNPs and haplotypes map of HLA region (4Mb)
in Chinese by 454 sequencing technology, establish MHC tagSNPs paltform
for association study on immune-related disease and population genetic
study. Polymorphisms in HLA are complicated; our study will provide
important data to the International Hapmap Project.
Principle of 454 sequencing technology
MHC genes in chromosome 6
3.Disease association study
We previously studied the association of HLA Polymorphisms
with HBV infection, endometriosis and cervical cancer based on sequence
based-typing method. We found DR4, DR7 and DR13 may be the resistant
genes in HBV infection; DQA1*0401 and DQA1*0301 may be the susceptible
and resistant genes of endometriosis, respectively; DQB1*060101,DQB1*050201
may be the susceptible and resistant genes of Cervical Cancer, respectively.
The disease association study of Ankylosing Spondylitis, IgA nephropathy
and Type-I diabetes is ongoing based on multiplex sites analysis
in whole genome instead of genotyping analysis on single locus.
High-resolution DNA melting analysis for SNPs genotyping