J Nutr Hum Health 2017 Volume 1 Issue 2
Page 25
July 24-26, 2017 | Vancouver, Canada
International conference on
DIABETES, NUTRITION, METABOLISM & MEDICARE
allied
academies
T
ype-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. Identifying these
genetic factors could contribute to developing new medical
treatments and tools to identify most at risk individuals.
Recently, a novel highly genetically diverse mouse resource
population, named the Collaborative Cross (CC), was
developed and aimed for studying complex traits, including
T2D. The CC mice have more genetic diversity than human
population. Here, we used this mouse population of mapping
Quantitative Trait Loci (QTL) underlying impaired glucose
tolerance phenotypic variations and associated diseases
including liver fat accumulation in CC mice. Furthermore,
we used Next generation RNA-sequencing (RNAseq) for
studying gene expression variations and alternative splicing
observation to identify genes that may underline the disease
development. Our results have shown significant variations
between the recorded phenotypes between the different
CC lines and a sex was observed. QTL mapping results have
identified number of small genomic regions associated with
the tested traits.
Methods:
A Cohort of 683 mice of 68 CC lines maintained on
high-fat (42%fat) diet (HFD) for 12weeks followedbybiweekly
bodyweight (BW), body length (BL), waist circumstance (WC),
and body mass index (BMI) were measured. Subsequently,
assessed by intraperitoneal glucose tolerance test (IPGTT),
and liver weight (electronic balance) and fattiness (DEXA
scanner) was assessed. Genomic DNA of the CC lines was
genotyped with high-density single nucleotide polymorphic
(SNP) markers and finally QTL mapping was conducted. Next
generation RNA-sequencing (RNAseq) was performed for
livers of diabetic and non-diabetic mice of CC lines following
12 weeks HFD, and DNA methylation assessed on blood for
testing epigenetic effect of HFD.
Results & Discussion:
Genome wide search for QTL analysis
has revealed number of significant QTL associated with
glucose tolerance test, which was defined as area under
curve (AUC), as well QTL underline fatty liver accumulation
as a results of T2D development. RNAseq approach of
hepatic gene expression analysis has identified significant
gene variations between the diabetic and no-diabetic mice,
as well between both sexes.
Biography
Fuad A Iraqi is a Molecular Geneticist and world leader in the area of dissecting com-
plex traits including hosts susceptibility to infection and chronic diseases. His current
research is focused on understanding diseases etiology and host susceptibility to in-
fectious and chronic diseases including type 2 diabetes and cardiovascular diseases
(CVD) associated with obesity, Klebsiella pneumonia, Aspergillus fumigatus, dental
infection (Periodontitis), and mapping modifiers for colon cancer development. His
research projects are important for better understanding the host susceptibility to va-
riety of infectious and chronic diseases, which will serve a step towards improving our
knowledge of specific and general pathways and network systems, which can lead to
establish better disease prevention and control strategies. He has studied for his BSc
(Biology), MSc (Biochemistry) and PhD (Molecular Genetics) at the Hebrew Univer-
sity at Jerusalem. He worked as a Postdoctoral for two years at the Hospital for Sick
Children at Toronto, Canada, and two more years at the USDA, ARS- East Lansing, MI,
before joining the International Livestock Research Institute (ILRI), based in Nairobi,
Kenya as Scientist. In 2007, he moved to his current position as Professor and Chairman
of the Department of Clinical Microbiology and Immunology, at the Faculty of Medicine
at Tel-Aviv University. He has more than 135 publications on per reviewed journals, and
more than 25 book chapters. His current H-Index is 27.
fuadi@post.tau.ac.ilFuad A Iraqi
Tel-Aviv University, Israel
Dissection the complexity of host susceptibility to type 2 diabetes development
and the pharmacogenetics dilemma