Research paper Analysis of ANKKI (rs1800497) and DRD2 (rs1079597, rs1800498) variants in five ethnic groups from Punjab, North-West India Gagandeep Singh a,b , Indu Talwar a , Rubina Sharma b , Harkirat Singh Sandhu b , Kawaljit Matharoo b, ⁎, A.J.S. Bhanwer b, ⁎ a Department of Anthropology, Panjab University, Chandigarh 160014, India b Department of Human Genetics, Guru Nanak Dev University, Amritsar 143005, Punjab, India abstract article info Article history: Received 18 November 2015 Received in revised form 12 February 2016 Accepted 7 March 2016 Available online 10 March 2016 Dopamine D2 receptor (DRD2) is one of the essential neurotransmitters in the brain studied extensively in the field of psychiatric disorders, alcoholic behaviors and Pharmacology. It is also a promising gene for studying the evolutionary and genetic variation among populations. The present study was an attempt to understand the extent of genetic variation among five different ethnic groups (Bania, Brahmin, Jat Sikh, Khatri and Scheduled caste) of Punjab (North West India). A total of 1012 individuals belonging to the above mentioned groups were analyzed for three TaqI Polymorphic loci of DRD2 and ankyrin repeat and kinase domain containing 1 (ANKKI) using the allele frequencies and haplotype frequency distribution pattern. All the three loci were found to be polymorphic among the studied populations. The average heterozygosity for all loci in these ethnic groups was fairly substantial ranging from 0.3936 to 0.4986. The genetic differentiation among the population was observed to be in order of 0.0053.Among of the eight studied haplotypes, only six were shared by all the ethnic groups. TaqID and TaqIB loci were reported to be in significantly higher linkage disequilibrium (LD) in Scheduled Caste only, whereas TaqIA and TaqID showed modest LD in Brahmin, Jat Sikh and Khatri. Multidimensional scaling analysis revealed that the studied ethnic groups formed a close cluster, suggesting similar genetic structure of these populations which are in close proximity with other Indo European speaking North Indian and western Indian population groups. Overall this study highlights the genomic uniformity among the ethnic groups of Punjab (North-West India) owing to their common ancestral history and geographical closeness. © 2016 Published by Elsevier B.V. Keywords: PCR-RFLP Linkage disequilibrium DRD2 gene ANKKI gene Haplotype North West India 1. Introduction Dopamine D2 receptor (DRD2) is one of the essential neurotransmit- ters in the brain and is a member of the rhodopsin family. DRD2 is re- ported to be a strong candidate gene implicated in behavioral disorders, alcoholism, obesity and other substance-use disorders (Noble et al., 1993; Blum et al., 1996; Lawford et al., 2000; Bhaskar et al., 2010; Singh et al., 2013). The three TaqI restriction loci of DRD2 (TaqIA, TaqIB and TaqID) have been studied previously in order to de- fine human genetic structure and migratory pattern among various human populations (Kidd et al., 1998; Chakrabarti et al., 2002; Vishwanathan et al., 2004). Out of these, TaqIA (rs1800497) located in 3′ flanking region of DRD2 has now been recognized as a functional cod- ing polymorphism of adjacent ankyrin repeat and kinase domain con- taining 1 (ANKKI) gene (Neville et al., 2004; Suchanecka et al., 2011). In various populations, these three loci have shown different pattern of pairwise linkage disequilibrium (LD) and this variation reflects the combined forces of genetic drift, admixture and selection that act over evolutionary time on these populations (Zhang et al., 2003). The knowl- edge of these genetic variants can be pivotal for understanding the com- plexities of the human evolution and population genetic structure. A global survey of DRD2 variants in 28 distinct populations (Kidd et al., 1998) showed that African populations have higher heterozygosity than non-African populations. Previous studies on DRD2 locus in India have been mainly restricted to Dravidian speaking South Indian popula- tion (Vishwanathan et al., 2004; Bhaskar et al., 2008; Prabhakaran et al., 2008; Saraswathy et al., 2009a), North Eastern population (Saraswathy et al., 2009b), Western Indian population (Kshatriya et al., 2010) and so far a single study has been reported from North Indian population (Saraswathy et al., 2010). However, no such study has been conducted on the ANKKI and DRD2 loci in the Indo-European speaking populations groups from Punjab. Gene 584 (2016) 69–74 Abbreviations: AMOVA, analysis of molecular variance; ANKKI, ankyrin repeat and kinase domain containing 1; DRD2, Dopamine D2 receptor; F ST , inter- population diversity; H S , Intra-population diversity; H T , total genomic diversity; LD, linkage disequilibrium; POPGENE, population genetic analysis program; PCR-RFLP, polymerase chain reaction- restriction fragment length polymorphism; SNP, single nucleotide polymorphism; MDS, multidimensional scaling. ⁎ Corresponding authors at: Department of Human Genetics, Guru Nanak Dev University, Amritsar, Punjab, India. E-mail addresses: matharookawal@gmail.com (K. Matharoo), ajsbhanwer@gmail.com (A.J.S. Bhanwer). http://dx.doi.org/10.1016/j.gene.2016.03.009 0378-1119/© 2016 Published by Elsevier B.V. Contents lists available at ScienceDirect Gene journal homepage: www.elsevier.com/locate/gene