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Title of Thesis

Aisha Mohyuddin
Institute/University/Department Details
Department of Biological Sciences/ Quaid-i-Azam University, Islamabad
Molecular Biology
Number of Pages
Keywords (Extracted from title, table of contents and abstract of thesis)
genetic diversity, pakistan, human leukocyte antigen, extreme polymorphism, hla-a, hla-b, hla-c, hla-drb, dqb1, polymerase chain reaction, sequence specific primers, allele frequencies

The human leukocyte antigen (HLA) system, present on chromosome 6 is one of the most extensively studied regions of the human genome. The most striking feature of the HLA system is the extreme polymorphism found at some of its loci. This characteristic of the HLA system has made it an invaluable tool for population genetics analyses. Different populations exhibit characteristic allele and haplotype frequencies, which provide information about their history, migration patterns, evolution, genetics, disease susceptibility and resistance. In this study the genetic polymorphism of seven Pakistani ethnic groups was investigated at the HLA-A, -B, -C, -DRB and DQB1 loci using polymerase chain reaction with sequence specific primers (PCR-SSP). The groups included in this study are the Baloch, Brahui, Sindhi and Parsi from the south and the Burusho, Kalash and Pathan from the north of Pakistan. The allele frequencies, three-locus haplotype frequencies for HLA-A, -C, -B and HLA-A, -B, -DRBl and two locus haplotype frequencies for HLA-A, -B, HLA-B, -C, HLA-B, -DRBl and HLA-DRBl, -DQBl along with linkage disequilibrium, relative linkage disequilibrium and their significance (p-value as determined by -l-test) were calculated. Neighbor joining trees based on allele frequencies were constructed and correspondence analysis was carried out. Variation in the allele and haplotype distribution between the seven Pakistani ethnic groups was observed. A phylogenetic tree and correspondence analysis based on HLA- A, -B, -C, -DRBl and -DQBl allele frequencies revealed the Kalash and Parsi populations to be distinct from each other and the remaining Pakistani populations. The Baloch and Brahui were closely related to one another. The Sindhi were closer to the Pathan and Burusho populations than to the neighboring Baloch and Brahui populations indicating admixture between the northern and southern populations of Pakistan. The three- and two- locus haplotypes reveal a large amount of admixture in the Pakistani populations. The haplotypes found in the Pakistani populations suggest an influence of Caucasian and Oriental populations. A phylogenetic tree and correspondence analysis comparing the Pakistani populations to various other world populations (HLA- A, -B and -C allele frequency data from the 11th and 12th International Histocompatibility Workshops) showed that the Pakistani ethnic groups, with the exception of the Parsi, lie within the cluster of the European and Asian Indian populations. The Parsi populations show a striking affinity to the Iraqi Jews, which is in accordance with historical records placing the origin of the Parsi in ancient Persia. These results not only help in studying the origins of the various Pakistani populations but also provide a background for a variety of applications including tissue typing and HLA and disease association studies in Pakistan.

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2577.71 KB
S. No. Chapter Title of the Chapters Page Size (KB)
1 0 Contents 0
141.18 KB
2 1 Introduction 1
55.86 KB
3 2 Review of Literature 7
214.77 KB
4 3 History of the Populations of Pakistan 25
160.86 KB
5 4 Materials and Methods 37
144.73 KB
6 5 Results 49
1053.36 KB
7 6 Discussion and Conclusions 123
1036.57 KB
  6.1 References 172