Identification of rare deleterious genetic variations in a Pakistani obese individual

Abstract

Obesity is one of the major health concerns globally, which is increasing the burden of other
lifestyle diseases. This study involves genome-wide finding of potentially deleterious variants
in an obese individual using NGS technology. The annotation of the sequencing data with
ANNOVAR, CADD, and VEP tools, emphasized multiple genetic risk factors for obesity,
Hyperlipidemia, and associated comorbidities. These analyses showed 425 missense SNVs
predicted as deleterious by SIFT, Polyphen2, and CADD, including a novel homozygous SNV
in obesity-associated 5-methyltetrahydrofolate-homocysteine methyltransferase reductase
(MTRR). Two protein truncating SNVs, heterozygous rs328 (p: Ser474X) in lipoprotein lipase
(LPL), and homozygous rs885985 (p: Glu37X) in Claudin 5 (CLDN5) were also found. By
comparing population allele frequencies, 11 predicted deleterious missense SNVs were found
to have higher allele frequency in South Asians compared to global populations of 1000
Genomes Project.