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whole-exome-sequencing
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Inferring the Demographic History of Iranian Populations from Whole Exome Sequencing Data
, M.Sc. Thesis Sharif University of Technology ; Motahari, Abolfazl (Supervisor) ; Khalaj, Babak (Supervisor)
Abstract
One of the cornerstones of population genetics is finding ancestral relations between people of a population. Mutations and recombinations are two major signals that can be exploited to infer the population ancestral relationships. Next Generation Sequencing (NGS) has paved the way for achieving this endeavor by providing massive data including single nucleotide polymorphisms, insertions, and deletions as well as structural variations between individuals. In this thesis, the goal is to infer the ancestral structure of a given gene from thousands of NGS datasets. We also attempt to decode times of important events including mutations and recombinations. To this end, we first split a gene into...
Wolfram-like syndrome with bicuspid aortic valve due to a homozygous missense variant in CDK13
, Article Journal of Human Genetics ; Volume 66, Issue 10 , 2021 , Pages 1009-1018 ; 14345161 (ISSN) ; Raza, S. I ; Zeeshan Anwar, M ; Bharadwaj, T ; Liaqat, K ; Khokhar, M. A. S ; Everard, J. L ; Nasir, A ; Nickerson, D. A ; Bamshad, M. J ; Ansar, M ; Schrauwen, I ; Ahmad, W ; Leal, S. M ; Sharif University of Technology
Springer Nature
2021
Abstract
Background: Wolfram syndrome (WFS) is characterized by deafness, diabetes mellitus, and diabetes insipidus along with optic atrophy. WFS has an autosomal recessive mode of inheritance and is due to variants in WFS1 and CISD2. Methods: We evaluated the underlying molecular etiology of three affected members of a consanguineous family with hearing impairment, bicuspid aortic valve, diabetes mellitus and insipidus, clinodactyly, and gastrointestinal tract abnormalities via exome sequencing approach. We correlated clinical and imaging data with the genetic findings and their associated phenotypes. Results: We identified a homozygous missense variant p.(Asn1097Lys) in CDK13, a gene previously...
Homozygous mutations in C14orf39/SIX6OS1 cause non-obstructive azoospermia and premature ovarian insufficiency in humans
, Article American Journal of Human Genetics ; Volume 108, Issue 2 , 2021 , Pages 324-336 ; 00029297 (ISSN) ; Jiao, Y ; Khan, R ; Jiang, X ; Javed, A. R ; Ali, A ; Zhang, H ; Zhou, J ; Naeem, M ; Murtaza, G ; Li, Y ; Yang, G ; Zaman, Q ; Zubair, M ; Guan, H ; Zhang, X ; Ma, H ; Jiang, H ; Ali, H ; Dil, S ; Shah, W ; Ahmad, N ; Zhang, Y ; Shi, Q ; Sharif University of Technology
Cell Press
2021
Abstract
Human infertility is a multifactorial disease that affects 8%–12% of reproductive-aged couples worldwide. However, the genetic causes of human infertility are still poorly understood. Synaptonemal complex (SC) is a conserved tripartite structure that holds homologous chromosomes together and plays an indispensable role in the meiotic progression. Here, we identified three homozygous mutations in the SC coding gene C14orf39/SIX6OS1 in infertile individuals from different ethnic populations by whole-exome sequencing (WES). These mutations include a frameshift mutation (c.204_205del [p.His68Glnfs∗2]) from a consanguineous Pakistani family with two males suffering from non-obstructive...
Genetic risk variants for class switching recombination defects in ataxia-telangiectasia patients
, Article Journal of Clinical Immunology ; 2021 ; 02719142 (ISSN) ; Mehrmohamadi, M ; Ranjouri, M. R ; Akrami, M ; Rezaei, N ; Saberi, A ; Yazdani, R ; Abolhassani, H ; Aghamohammadi, A ; Sharif University of Technology
Springer
2021
Abstract
Background: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. A-T patients manifest considerable variability in clinical and immunological features, suggesting the presence of genetic modifying factors. A striking heterogeneity has been observed in class switching recombination (CSR) in A-T patients which cannot be explained by the severity of ATM mutations. Methods: To investigate the cause of variable CSR in A-T patients, we applied whole-exome sequencing (WES) in 20 A-T patients consisting of 10 cases with CSR defect (CSR-D) and 10 controls with normal CSR (CSR-N). Comparative analyses on modifier...
Genetic risk variants for class switching recombination defects in ataxia-telangiectasia patients
, Article Journal of Clinical Immunology ; Volume 42, Issue 1 , 2022 , Pages 72-84 ; 02719142 (ISSN) ; Mehrmohamadi, M ; Ranjouri, M. R ; Akrami, S. M ; Rezaei, N ; Saberi, A ; Yazdani, R ; Abolhassani, H ; Aghamohammadi, A ; Sharif University of Technology
Springer
2022
Abstract
Background: Ataxia-telangiectasia (A-T) is a rare autosomal recessive disorder caused by mutations in the ataxia telangiectasia mutated (ATM) gene. A-T patients manifest considerable variability in clinical and immunological features, suggesting the presence of genetic modifying factors. A striking heterogeneity has been observed in class switching recombination (CSR) in A-T patients which cannot be explained by the severity of ATM mutations. Methods: To investigate the cause of variable CSR in A-T patients, we applied whole-exome sequencing (WES) in 20 A-T patients consisting of 10 cases with CSR defect (CSR-D) and 10 controls with normal CSR (CSR-N). Comparative analyses on modifier...
A novel variant in TLE6 is associated with embryonic developmental arrest (EDA) in familial female infertility
, Article Scientific Reports ; Volume 12, Issue 1 , 2022 ; 20452322 (ISSN) ; Mohebi, M ; Berjis, K ; Ghahremani, A ; Modarresi, M. H ; Ghafouri Fard, S ; Sharif University of Technology
Nature Research
2022
Abstract
This study aims to identify genetic causes of familial female infertility characterized by embryonic developmental arrest (EDA) and repeated implantation failure (RIF) with oocyte donation IVF cycle. We used Whole-exome sequencing and Sanger validation to find causative genes in an Iranian consanguineous family that had 3 infertile daughters, 4 fertile daughters, and 2 fertile sons. All patients in this consanguineous family exhibited typical manifestations of unexplained RIF and EDA. Genetic analysis identified a homozygous missense variant (c.G1054C:p.G352R) in exon 13 of the TLE6 gene that cosegregated with the EDA phenotype in an autosomal recessive pattern. Other members of the family,...