Whole Exome Sequencing Study in a Family with Type 2 Diabetes Mellitus

Xiaowei Zhou; Weichang Guo; Hejia Yin; Jie Chen; Liju Ma; Qiuping Yang; Yan Zhao; Shaoyou Li; Weijun Liu; Huifang Li

doi:10.2147/IJGM.S335090

Whole Exome Sequencing Study in a Family with Type 2 Diabetes Mellitus

Int J Gen Med. 2021 Nov 16:14:8217-8229. doi: 10.2147/IJGM.S335090. eCollection 2021.

Authors

Xiaowei Zhou^#¹, Weichang Guo^#², Hejia Yin¹, Jie Chen¹, Liju Ma³, Qiuping Yang⁴, Yan Zhao¹, Shaoyou Li⁵, Weijun Liu¹, Huifang Li¹

Affiliations

¹ Department of Diabetes, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
² Department of Physical Education, Kunming Medical University, Kunming, People's Republic of China.
³ Department of Clinical Laboratory, First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
⁴ Department of Geriatrics, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.
⁵ Department of NHC Key Laboratory of Drug Addiction Medicine, The First Affiliated Hospital of Kunming Medical University, Kunming, People's Republic of China.

^# Contributed equally.

Abstract

Background: Type 2 diabetes mellitus (T2DM) is characterized by β cell decline in the pancreas and insulin resistance. This study aimed to investigate the possible pathogenic gene mutation sites of T2DM patients using whole exome sequencing.

Materials and methods: We recruited a Chinese family with 3-generation history of diabetes. The whole blood genomic DNA of seven members of the family was extracted and sent for whole exome sequencing. Biological information was analyzed with in silico prediction methods, including significance analysis of single nucleotide polymorphism (SNP)/Indel site, and analysis of specific SNP/Indel proteins and their potential mechanisms.

Results: Six out of seven members of the family were diagnosed with diabetes. All DNA samples (23 kb) met quality requirements of library construction. Clean reads of each sample demonstrated high Q20 and Q30 (>80%), indicating good sequencing quality of sequencing data. A total of 130,693 SNPs and 15,928 Indels were found in DNA samples. A total of 22 significant SNPs and Indel mutation sites located on 19 genes were obtained, including ZCCHC3, SYN2, RPL14, SRRD, AMD1, CAMKK2, ZNF787, RNF157, NPIPB15, ALG3, KIAA0040, MAST2, ESRRA, C8orf58, PNLIPRP1, DACH1, MACC1, CAPN9 and DMKN. An rs2305205 mutation of PNLIPRP1 gene and an rs778701848 mutation of CAMKK2 gene may be associated with the pathogenesis of T2DM in this family.

Conclusion: Exons of these diabetic patients demonstrated an rs2305205 mutation in PNLIPRP1 gene and an rs778701848 mutation in CAMKK2 gene. These two mutations might promote T2DM occurrence through reducing sensitivity of peripheral tissue to insulin and reducing insulin secretion.

Keywords: CAMKK2; PNLIPRP1; gene mutation; type 2 diabetes; whole exome sequencing.

Grants and funding

The study was supported by grants from the National Natural Science Fund of China (Grant No. 81160104, 30760087and 82160165), the Yunnan provincial science and technology department-Kunming medical University applied basic research joint project [Grant No. 2018FE001 (−043)], the Training plan for medical discipline leaders of Yunnan provincial health and family planning commission (Grant No. D-2017039) and The young and middle-aged academic and technical leaders reserve talented person project in yunnan province (Grant NO. 202105AC160093).