Glucose tolerance female-specific QTL mapped in collaborative cross mice.
Type-2 diabetes (T2D) is a complex metabolic disease characterized by impaired glucose tolerance. Despite environmental high risk factors, host genetic background is a strong component of T2D development. Herein, novel highly genetically diverse strains of collaborative cross (CC) lines from mice were assessed to map quantitative trait loci (QTL) associated with variations of glucose-tolerance response. In total, 501 mice of 58 CC lines were maintained on high-fat (42 % fat) diet for 12 weeks. Thereafter, an intraperitoneal glucose tolerance test (IPGTT) was performed for 180 min. Subsequently, the values of Area under curve for the glucose at zero and 180 min (AUC0-180), were measured, and used for QTL mapping. Heritability and coefficient of variations in glucose tolerance (CVg) were calculated. One-way analysis of variation was significant (P < 0.001) for AUC0-180between the CC lines as well between both sexes. Despite Significant variations for both sexes, QTL analysis was significant, only for females, reporting a significant female-sex-dependent QTL (~2.5 Mbp) associated with IPGTT AUC0-180trait, located on Chromosome 8 (32-34.5 Mbp, containing 51 genes). Gene browse revealed QTL for body weight/size, genes involved in immune system, and two main protein-coding genes involved in the Glucose homeostasis, Mboat4 and Leprotl1. Heritability and coefficient of genetic variance (CVg) were 0.49 and 0.31 for females, while for males, these values 0.34 and 0.22, respectively. Our findings demonstrate the roles of genetic factors controlling glucose tolerance, which significantly differ between sexes requiring independent studies for females and males toward T2D prevention and therapy.
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel.
Hanifa J
HJ
Abu-Toamih Atamni
The Blavatnik School of Computer Science, Tel-Aviv University, Tel Aviv, Israel.
Yaron
Y
Ziner
Department of Genetics, University Collage of London, London, UK.
Richard
R
Mott
The Blavatnik School of Computer Science, Tel-Aviv University, Tel Aviv, Israel.
Lior
L
Wolf
Department of Clinical Microbiology and Immunology, Sackler Faculty of Medicine, Tel-Aviv University, Ramat Aviv, 69978, Tel Aviv, Israel. fuadi@post.tau.ac.il.
Fuad A
FA
Iraqi
D000217:Acyltransferases / Q000235:genetics*; D000818:Animals; D001786:Blood Glucose / Q000235:genetics; D001835:Body Weight / Q000235:genetics; D002874:Chromosome Mapping; D003433:Crosses, Genetic; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005260:Female; D014644:Genetic Variation; D005947:Glucose / Q000235:genetics / Q000378:metabolism; D005951:Glucose Tolerance Test; D008297:Male; D051379:Mice; D010641:Phenotype; D040641:Quantitative Trait Loci / Q000235:genetics*; D054411:Receptors, Leptin / Q000235:genetics*
D001786:Blood Glucose; D054411:Receptors, Leptin; D000217:Acyltransferases; D005947:Glucose