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      Human leukocyte antigen alleles, genotypes and haplotypes frequencies in renal transplant donors and recipients from West Central India

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          Abstract

          BACKGROUND:

          Human leukocyte antigen (HLA) is comprised of a highly polymorphic set of genes which determines the histocompatibility of organ transplantation. The present study was undertaken to identify HLA class I and class II allele, genotype and haplotype frequencies in renal transplant recipients and donors from West Central India.

          MATERIALS AND METHODS:

          HLA typing was carried out using Polymerase Chain Reaction-Sequence Specific Primer in 552 live related and unrelated renal transplant recipients and donors.

          RESULTS:

          The most frequent HLA class I and class II alleles and their frequencies in recipients were HLA-AFNx0101 (0.1685) and AFNx0102 (0.1649), HLA-BFNx0135 (0.1322), and HLA-DR beta 1 (DRB 1)FNx0115 (0.2192), whereas in donors, these were HLA-AFNx0102 (0.1848) and AFNx0101 (0.1667), HLA-BFNx0135 (0.1359), and HLA-DRB1FNx0115 (0.2409). The two-locus haplotype statistical analysis revealed HLA-AFNx0102-B61 as the most common haplotype with the frequency of 0.0487 and 0.0510 in recipients and donors, respectively. Further, among the three locus haplotypes HLA-AFNx0133-BFNx0144-DRB1FNx0107 and HLA-AFNx0102-BFNx0161-DRB1FNx0115 were the most common haplotypes with frequencies 0.0362 and 0.0326, respectively in recipients and 0.0236 and 0.0323, respectively in donors. Genotype frequency revealed a high prevalence of genotype HLA-AFNx0102/AFNx0124 in recipients (0.058) compared to donors (0.0109) whereas low prevalence of HLA-AFNx0101/AFNx0102 in recipients (0.0435) than in donors (0.0797). The phylogenetic and principal component analysis of HLA allele and haplotype frequency distribution revealed genetic similarities of various ethnic groups. Further, case control analysis provides preliminary evidence of association of HLA-A genotype ( P < 0.05) with renal failure.

          CONCLUSION:

          This study will be helpful in suitable donor search besides providing valuable information for population genetics and HLA disease association analysis.

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          Most cited references23

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          A rapid procedure for extracting genomic DNA from leukocytes.

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            Human leukocyte antigen gene polymorphism and the histocompatibility laboratory.

            The human leukocyte antigens (HLA) encoded by genes within the major histocompatibility complex display an impressive degree of polymorphism. This variability is apparently maintained in human populations through the need to successfully display a wide range of processed foreign peptides to the T cell antigen receptor. The large number of alleles at the Class I and Class II loci pose a significant problem for molecular diagnosis. Knowledge of allele groups and specific alleles present in individuals has important implications in organ and stem cell transplantation and in disease association studies. Histocompatibility laboratories have transformed themselves during the past decade as they have adapted the techniques of molecular diagnostics to the challenge of identifying HLA alleles.
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              The haplotype structure of the human major histocompatibility complex.

              There is great interest in the use of single-nucleotide polymorphisms (SNPs) and linkage disequilibrium (LD) analysis to localize human disease genes. The results suggest that the human genome, including the major histocompatibility complex (MHC), consists largely of 5- to 200-kb blocks of sequence fixity between which random recombination occurs. Direct determination of MHC haplotypes from family studies also demonstrates similar-sized blocks, but otherwise gives a very different picture, with a third to a half of Caucasian haplotypes fixed from HLA-B to HLA-DR/DQ (at least 1 Mb) as conserved extended haplotypes (CEHs), some of which encompass more than 3 Mb. These fixed haplotypes differ in frequency both in different Caucasian subpopulations and in Caucasian patients with HLA-associated diseases, complicating disease susceptibility gene localization. The inherent inability of LD analysis to "see" DNA fixity beyond three markers contributes to the failure of SNP/LD analysis to define in detail or even detect CEHs in the MHC and probably elsewhere in the genome. More importantly, the use of statistical analysis, rather than direct haplotype determination and counting, fails to reveal the details of haplotype structure essential for gene localization. Given the oversimplified picture of the MHC (and probably the rest of the genome) provided only by SNP/LD-defined blocks, it is questionable whether this approach will be of great help in disease susceptibility gene localization or identification.
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                Author and article information

                Journal
                Indian J Hum Genet
                Indian J Hum Genet
                IJHG
                Indian Journal of Human Genetics
                Medknow Publications & Media Pvt Ltd (India )
                0971-6866
                1998-362X
                Apr-Jun 2013
                : 19
                : 2
                : 219-232
                Affiliations
                [1]Department of Animal Biotechnology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand, Gujarat, India
                [1 ]Department of Nephrology, Muljibhai Patel Urological Hospital, Nadiad, Gujarat, India
                Author notes
                Address for correspondence: Prof. Chaitanya G. Joshi, Department of Animal Biotechnology, College of Veterinary Science and Animal Husbandry, Anand Agricultural University, Anand - 388 001, Gujarat, India. E-mail: cgjoshi@ 123456rediffmail.com
                Article
                IJHG-19-219
                10.4103/0971-6866.116122
                3758731
                24019626
                0d82f225-1e3d-4618-a91a-4f1bf06e1eee
                Copyright: © Indian Journal of Human Genetics

                This is an open-access article distributed under the terms of the Creative Commons Attribution-Noncommercial-Share Alike 3.0 Unported, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                Categories
                Original Article

                Genetics
                allele,genotype,haplotype,human leukocyte antigens frequencies,polymorphism,renal transplant
                Genetics
                allele, genotype, haplotype, human leukocyte antigens frequencies, polymorphism, renal transplant

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