Molecular dynamics of MHC genesis unraveled by sequence analysis of the 1,796,938-bp HLA class I region.
نویسندگان
چکیده
The intensely studied MHC has become the paradigm for understanding the architectural evolution of vertebrate multigene families. The 4-Mb human MHC (also known as the HLA complex) encodes genes critically involved in the immune response, graft rejection, and disease susceptibility. Here we report the continuous 1,796,938-bp genomic sequence of the HLA class I region, linking genes between MICB and HLA-F. A total of 127 genes or potentially coding sequences were recognized within the analyzed sequence, establishing a high gene density of one per every 14.1 kb. The identification of 758 microsatellite provides tools for high-resolution mapping of HLA class I-associated disease genes. Most importantly, we establish that the repeated duplication and subsequent diversification of a minimal building block, MIC-HCGIX-3.8-1-P5-HCGIV-HLA class I-HCGII, engendered the present-day MHC. That the currently nonessential HLA-F and MICE genes have acted as progenitors to today's immune-competent HLA-ABC and MICA/B genes provides experimental evidence for evolution by "birth and death," which has general relevance to our understanding of the evolutionary forces driving vertebrate multigene families.
منابع مشابه
Molecular Typing by Polymerase Chain Reaction Sequence Specific Primers (PCR- SSP) of Human Leukocyte Class I and Class II Alleles in a Sample of Iraqi Visceral Leishmaniasis Patients
Objective: This study aimed to investigate the association between HLA alleles and visceral leishmaniasis (VL) in a sample of Iraqi patients. Methods: A total of 30 patients were studied, in addition to 20 age, gender and ethnicity matched controls. All subjects were genotyped by polymerase chain reaction-sequence specific primers (PCR-SSP) method. Results: For HLA-class I region (A and B loci)...
متن کاملMolecular Typing by Polymerase Chain Reaction Sequence Specific Primers (PCR- SSP) of Human Leukocyte Class I and Class II Alleles in a Sample of Iraqi Visceral Leishmaniasis Patients
Objective: This study aimed to investigate the association between HLA alleles and visceral leishmaniasis (VL) in a sample of Iraqi patients. Methods: A total of 30 patients were studied, in addition to 20 age, gender and ethnicity matched controls. All subjects were genotyped by polymerase chain reaction-sequence specific primers (PCR-SSP) method. Results: For HLA-class I region (A and B loci)...
متن کاملHLA Class I Gene Polymorphism in Iranian Patients with Papillon-Lefevre Syndrome
Background: Papillon-Lefevre Syndrome (PLS) is a rare autosomal recessive disorder characterized by diffused palmoplantar keratoderma and severe periodontitis. Increased susceptibility to infections due to impairment of the immune system is considered to be involved in pathoetiology of this disease. Objective: According to the crucial function of HLA molecules in immune responses and associati...
متن کاملComparative genome organization of human, murine, and feline MHC class II region.
To study comparative molecular dynamics in the genesis of the major histocompatibility complex (MHC), we determined a complete nucleotide sequence spanning 758,291 bp of the domestic cat (Felis catus) extended and classical class II region. The feline class II MHC includes 44 genes (31 predicted to be expressed) which display DNA sequence homology and ordered gene synteny with human HLA and mou...
متن کاملTyping of HLA Class I by Polymerase Chain Reaction-Sequence Specific Oligonucleotide Primer (PCR-SSOP) Technique in Iranian Cord Blood Donors
Background: HLA compatibility between transplant donor and recipient is one of the major determinants of transplant outcome. Objective: To determine HLA class I by PCR- Sequence-Specific Oligonucleotide Probe (PCR-SSOP) in cord blood donors. Methods: Genomic DNA of 142 cord blood samples registered at the Cord Blood Bank of Iran at Hematology, Oncology, and Bone Marrow Transplantation Researc...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 96 23 شماره
صفحات -
تاریخ انتشار 1999