Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans.
Genome-wide analysis of copy number variants and normal facial variation in a large cohort of Bantu Africans.
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DOI：
10.1016/j.xhgg.2021.100082
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发表时间：
2022-01-13
期刊：
影响因子：
--
通讯作者：
Hendricks AE
中科院分区：
文献类型：
--
作者：
Null M;Yilmaz F;Astling D;Yu HC;Cole JB;Hallgrímsson B;Santorico SA;Spritz RA;Shaikh TH;Hendricks AE
亲属之间面部特征的相似性表明，面部变异的基础是一个强大的遗传成分。虽然已经有许多关于面部异常遗传学的研究，最近，正常面部变异的单核苷酸多态性（SNP）全基因组关联研究（GWAS），但对遗传结构变异在决定面部形状中的作用知之甚少。在非洲班图儿童的样本中，我们发现只有9%的常见拷贝数变异（CNV）和10 kb CNV分析窗口被SNP很好地标记（r2 ≥ 0.8），这表明与我们内部称为CNV的关联没有被以前基于SNP的GWAS捕获。在这里，我们提出了一个GWAS和基因集分析正常的面部变异和CNVs之间的关系在一个样本的班图非洲儿童。我们报告了p值≤ 9.35 × 10−6的前五个区域，并在先前基于SNP的GWAS中确定的三个区域中发现了独立CNV关联的名义证据（p < 0.05）。CNV区域的相关性最强（p = 1.16 × 10−6，55个缺失和7个获得），包含NFATC 1，它与面部形态发生和巨颌症（一种涉及异常下面部发育的综合征）有关。该区域的基因组缺失与较小的平均下面部深度相关。重要的是，在基于SNP的GWAS中没有发现新的基因座，这表明CNVs可能参与决定面部形状的变化。鉴于基于SNP的GWAS过多，从现有数据中调用CNV可能是一种相对廉价的方法来帮助研究复杂的性状。
Similarity in facial characteristics between relatives suggests a strong genetic component underlies facial variation. While there have been numerous studies of the genetics of facial abnormalities and, more recently, single nucleotide polymorphism (SNP) genome-wide association studies (GWASs) of normal facial variation, little is known about the role of genetic structural variation in determining facial shape. In a sample of Bantu African children, we found that only 9% of common copy number variants (CNVs) and 10-kb CNV analysis windows are well tagged by SNPs (r2 ≥ 0.8), indicating that associations with our internally called CNVs were not captured by previous SNP-based GWASs. Here, we present a GWAS and gene set analysis of the relationship between normal facial variation and CNVs in a sample of Bantu African children. We report the top five regions, which had p values ≤ 9.35 × 10−6 and find nominal evidence of independent CNV association (p < 0.05) in three regions previously identified in SNP-based GWASs. The CNV region with strongest association (p = 1.16 × 10−6, 55 losses and seven gains) contains NFATC1, which has been linked to facial morphogenesis and Cherubism, a syndrome involving abnormal lower facial development. Genomic loss in the region is associated with smaller average lower facial depth. Importantly, new loci identified here were not identified in a SNP-based GWAS, suggesting that CNVs are likely involved in determining facial shape variation. Given the plethora of SNP-based GWASs, calling CNVs from existing data may be a relatively inexpensive way to aid in the study of complex traits.
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DOI：
10.1093/bioinformatics/btq033
发表时间：
2010-03-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Quinlan AR;Hall IM
通讯作者：
Hall IM
影响因子：
14.9
作者：
Frankish A;Diekhans M;Ferreira AM;Johnson R;Jungreis I;Loveland J;Mudge JM;Sisu C;Wright J;Armstrong J;Barnes I;Berry A;Bignell A;Carbonell Sala S;Chrast J;Cunningham F;Di Domenico T;Donaldson S;Fiddes IT;García Girón C;Gonzalez JM;Grego T;Hardy M;Hourlier T;Hunt T;Izuogu OG;Lagarde J;Martin FJ;Martínez L;Mohanan S;Muir P;Navarro FCP;Parker A;Pei B;Pozo F;Ruffier M;Schmitt BM;Stapleton E;Suner MM;Sycheva I;Uszczynska-Ratajczak B;Xu J;Yates A;Zerbino D;Zhang Y;Aken B;Choudhary JS;Gerstein M;Guigó R;Hubbard TJP;Kellis M;Paten B;Reymond A;Tress ML;Flicek P
通讯作者：
Flicek P
影响因子：
64.8
作者：
Sudmant PH;Rausch T;Gardner EJ;Handsaker RE;Abyzov A;Huddleston J;Zhang Y;Ye K;Jun G;Fritz MH;Konkel MK;Malhotra A;Stütz AM;Shi X;Casale FP;Chen J;Hormozdiari F;Dayama G;Chen K;Malig M;Chaisson MJP;Walter K;Meiers S;Kashin S;Garrison E;Auton A;Lam HYK;Mu XJ;Alkan C;Antaki D;Bae T;Cerveira E;Chines P;Chong Z;Clarke L;Dal E;Ding L;Emery S;Fan X;Gujral M;Kahveci F;Kidd JM;Kong Y;Lameijer EW;McCarthy S;Flicek P;Gibbs RA;Marth G;Mason CE;Menelaou A;Muzny DM;Nelson BJ;Noor A;Parrish NF;Pendleton M;Quitadamo A;Raeder B;Schadt EE;Romanovitch M;Schlattl A;Sebra R;Shabalin AA;Untergasser A;Walker JA;Wang M;Yu F;Zhang C;Zhang J;Zheng-Bradley X;Zhou W;Zichner T;Sebat J;Batzer MA;McCarroll SA;1000 Genomes Project Consortium;Mills RE;Gerstein MB;Bashir A;Stegle O;Devine SE;Lee C;Eichler EE;Korbel JO
通讯作者：
Korbel JO
影响因子：
4.5
作者：
Cole JB;Manyama M;Kimwaga E;Mathayo J;Larson JR;Liberton DK;Lukowiak K;Ferrara TM;Riccardi SL;Li M;Mio W;Prochazkova M;Williams T;Li H;Jones KL;Klein OD;Santorico SA;Hallgrimsson B;Spritz RA
通讯作者：
Spritz RA
影响因子：
4.4
作者：
Nyangiri, Oscar A.;Noyes, Harry;Matovu, Enock
通讯作者：
Matovu, Enock