Abidin, Nur Waliyuddin Hanis Zainal
(2018)
Understanding the genetic history of the Malay and Orang Asli populations in Peninsular Malaysia by killer cell immunolobulin-like receptors (KIR).
Masters thesis, Universiti Sains Malaysia.
Abstract
Extensive diversity of killer cell immunoglobulin-like receptor (KIR) genes
among diverse populations has made these immune genes become a potential
anthropological marker. The variations of KIR allotypes between two randomly
selected individuals are also useful in individual identification. Here, we genotyped
KIR genes content and allelic polymorphisms for the first time for Malay and Orang
Asli (OA) populations in Peninsular Malaysia using polymerase chain reactionsequence
specific primers (PCR-SSP), next-generation sequencing (NGS) and finally
optimized by Sanger typing method. A total of 333 individuals representing 10
Malay subethnic groups (Aceh, Banjar, Bugis, Jawa, Champa, Kedah, Kelantan,
Mandailing, Minangkabau and Patani) and 167 individuals from six OA subgroups
(Batek, Kensiu, Lanoh, Che Wong, Semai and Orang Kanaq) have participated in
this research. Fourty KIR genotypes were observed among Malays and 25 genotypes
in OA populations. Generally, the Malays having homogenous haplotype profile
with slightly high frequencies of haplotype A, whereas OA are heterogeneous with
various genotypes and wide range of haplotypes. Based on the principal component
analysis, the Malay subethnic groups are located between the Chinese, Indian and
Orang Asli populations. The Semang subgroups show genetic affinity toward the
Australian Aborigines, Papuan, Indian and African populations. They shared several
unique genotypes (AB6, BB71, BB73 and BB159) and have high frequencies ofHaplotype B, which could be speculated as general features of ancient populations.
The Senoi demonstrated high frequency of haplotype A, and expressing hybrid
phenotypes between Indo-China tribes and Semang population. In contrast, Orang
Kanaq, the only Proto-Malay subgroup studied is significantly different from both
related Taiwanese/Chinese and neighboring Malayo-Polynesian speaking
populations and show evidence of becoming a distinct population. The NGS has
successfully characterized 302 different allotypes of seven studied KIR genes among
Malay and OA populations. KIR2DL1, KIR2DL4, and KIR3DL3 genes show less
allelic variations and in favor on particular allele, which possibly being affected by
natural selection and creates selective sweep. In addition, KIR2DS4, KIR3DL1,
KIR3DL2 and KIR2DL3 are highly polymorphic genes with considerable number of
alleles discovered, suggesting that these genes evolved on balanced selection. The
KIR3DL2 gene could be the best marker for population studies, as it comprises
signature alleles (KIR3DL2*001 and *002) that support the theory of modern human
migration. Comprehensive datasets generated from this research demonstrate the
value of KIR genes content and allelic polymorphisms in elucidating genetic
relationships between the Malays and OA with other world populations.
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