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A linkage and exome study implicates rare variants of KANK4 and CAP2 in bipolar disorder in a multiplex family
Author(s) -
Anjanappa Ram M.,
Nayak Sourav,
Moily Nagaraj S.,
Manduva Vallikiran,
Nadella Ravi K.,
Viswanath Biju,
Reddy Yemmiganur C. J.,
Jain Sanjeev,
Anand Anuranjan
Publication year - 2020
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12815
Subject(s) - genetics , bipolar disorder , genetic linkage , candidate gene , exome sequencing , exome , chromosome 18 , biology , linkage (software) , chromosome , gene , mutation , cognition , neuroscience
Objectives Bipolar disorder (BD) is a neuropsychiatric disorder with a complex pattern of inheritance. Although many genetic studies have been conducted on BD, its genetic correlates remain uncertain. This study was aimed at identifying the genetic underpinnings of the disorder in an Indian family, which has been under comprehensive clinical evaluation and follow‐up for over 12 years. Methods We analysed a four‐generation family with several of its members diagnosed for BD employing a combination of genetic linkage and exome analysis . Results We obtained suggestive LOD score for a chromosome 1 and a chromosome 6 marker (D1S410; LOD = 3.01, Ө = 0; and D6S289; LOD = 1.58, Ө = 0). Manual haplotyping of the regions encompassing these two markers helped delimit a critical genomic interval of 32.44 Mb (D1S2700‐D1S435; chromosome 1p31.1‐13.2) and another of 10.34 Mb (D6S470‐D6S422; chromosome 6p22.3‐22.2). We examined the exomic sequences corresponding to these two intervals and found rare variants, NM_181712.4: c.2461G>T (p.Asp821Tyr) in KANK4 at 1p31.1‐13.2; and NM_006366:c.‐93G>A, in the 5' UTR of CAP2 at 6p22.3‐22.2. Conclusions Our studysuggests involvement of KANK4 or CAP2 or both in BD in this family. Further analysis of these two genes in BD patients and functional evaluation of the allelic variants identified are suggested.