Analysis of sequence data to identify potential risk variants for oral clefts in multiplex families

被引：9

作者：

Holzinger, Emily R. ^{[1
,2
]}

Li, Qing ^{[1
]}

Parker, Margaret M. ^{[3
,4
]}

Hetmanski, Jacqueline B. ^{[5
]}

Marazita, Mary L. ^{[6
]}

Mangold, Elisabeth ^{[7
]}

Ludwig, Kerstin U. ^{[7
,8
]}

Taub, Margaret A. ^{[9
]}

Begum, Ferdouse ^{[5
]}

Murray, Jeffrey C. ^{[10
]}

Albacha-Hejazi, Hasan ^{[11
]}

Alqosayer, Khalid ^{[12
]}

Al-Souki, Giath ^{[13
]}

Hejazi, Abdullatiff Albasha ^{[14
]}

Scott, Alan F. ^{[15
,16
]}

Beaty, Terri H. ^{[5
]}

Bailey-Wilson, Joan E. ^{[1
]}

机构：

[1] NHGRI, Computat & Stat Genom Branch, NIH, Baltimore, MD USA

[2] NIGMS, NIH, Bethesda, MD USA

[3] Brigham & Womens Hosp, Channing Div Network Med, 75 Francis St, Boston, MA 02115 USA

[4] Harvard Med Sch, Cambridge, MA USA

[5] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA

[6] Univ Pittsburgh, Sch Maryland Dent Med, Ctr Craniofacial & Dent Genet, Dept Oral Biol, Pittsburgh, PA USA

[7] Univ Bonn, Inst Human Genet, Bonn, Germany

[8] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany

[9] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Biostat, Baltimore, MD USA

[10] Univ Iowa, Dept Pediat, Iowa City, IA 52242 USA

[11] Hejazi Clin, Damascus, Syria

[12] Prime Hlth Clin, Jeddah, Saudi Arabia

[13] Saudi Red Crescent, Jeddah, Saudi Arabia

[14] Al Eqtisad Est, Jeddah, Saudi Arabia

[15] Johns Hopkins Sch Med, Ctr Inherited Dis Res, Baltimore, MD USA

[16] Johns Hopkins Sch Med, Inst Genet Med, Baltimore, MD USA

来源：

MOLECULAR GENETICS & GENOMIC MEDICINE | 2017年 / 5卷 / 05期

基金：

美国国家卫生研究院;

关键词：

DNA sequence data analysis; genetic risk variants; oral clefts; rare variants; statistical genetics; WIDE LINKAGE SCAN; GENOME SCAN; PALATE; LIP; MUTATIONS; LOCI; FRAMEWORK; GENES;

D O I：

10.1002/mgg3.320

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

BackgroundNonsyndromic oral clefts are craniofacial malformations, which include cleft lip with or without cleft palate. The etiology for oral clefts is complex with both genetic and environmental factors contributing to risk. Previous genome-wide association (GWAS) studies have identified multiple loci with small effects; however, many causal variants remain elusive. MethodsIn this study, we address this by specifically looking for rare, potentially damaging variants in family-based data. We analyzed both whole exome sequence (WES) data and whole genome sequence (WGS) data in multiplex cleft families to identify variants shared by affected individuals. ResultsHere we present the results from these analyses. Our most interesting finding was from a single Syrian family, which showed enrichment of nonsynonymous and potentially damaging rare variants in two genes: CASP9 and FAT4. ConclusionNeither of these candidate genes has previously been associated with oral clefts and, if confirmed as contributing to disease risk, may indicate novel biological pathways in the genetic etiology for oral clefts.

引用

页码：570 / 579

页数：10

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