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. 2019 Mar 15;28(6):1038-1051.
doi: 10.1093/hmg/ddy402.

Genomic analyses in African populations identify novel risk loci for cleft palate

Azeez Butali  1 , Peter A Mossey  2 , Wasiu L Adeyemo  3 , Mekonen A Eshete  4 , Lord J J Gowans  5 , Tamara D Busch  1 , Deepti Jain  6 , Wenjie Yu  7 , Liu Huan  8 , Cecelia A Laurie  6 , Cathy C Laurie  6 , Sarah Nelson  6 , Mary Li  1 , Pedro A Sanchez-Lara  9 , William P Magee  10 , Kathleen S Magee  11 , Allyn Auslander  10 , Frederick Brindopke  10 , Denise M Kay  12 , Michele Caggana  12 , Paul A Romitti  13 , James L Mills  14 , Rosemary Audu  15 , Chika Onwuamah  15 , Ganiyu O Oseni  16 , Arwa Owais  17 , Olutayo James  3 , Peter B Olaitan  16 , Babatunde S Aregbesola  18 , Ramat O Braimah  19 , Fadekemi O Oginni  18 , Ayodeji O Oladele  18 , Saidu A Bello  20 , Jennifer Rhodes  21 , Rita Shiang  21 , Peter Donkor  5 , Solomon Obiri-Yeboah  5 , Fareed Kow Nanse Arthur  5 , Peter Twumasi  5 , Pius Agbenorku  5 , Gyikua Plange-Rhule  5 , Alexander Acheampong Oti  5 , Olugbenga M Ogunlewe  3 , Afisu A Oladega  3 , Adegbayi A Adekunle  3 , Akinwunmi O Erinoso  3 , Olatunbosun O Adamson  3 , Abosede A Elufowoju  3 , Oluwanifemi I Ayelomi  3 , Taiye Hailu  4 , Abiye Hailu  4 , Yohannes Demissie  4 , Miliard Derebew  4 , Steve Eliason  7 , Miguel Romero-Bustillous  7 , Cynthia Lo  1 , James Park  1 , Shaan Desai  1 , Muiawa Mohammed  1 , Firke Abate  4 , Lukman O Abdur-Rahman  22 , Deepti Anand  23 , Irfaan Saadi  24 , Abimibola V Oladugba  25 , Salil A Lachke  23 , Brad A Amendt  7 , Charles N Rotimi  26 , Mary L Marazita  27 , Robert A Cornell  7 , Jeffrey C Murray  28 , Adebowale A Adeyemo  26
Affiliations

Genomic analyses in African populations identify novel risk loci for cleft palate

Azeez Butali et al. Hum Mol Genet. .

Erratum in

Abstract

Orofacial clefts are common developmental disorders that pose significant clinical, economical and psychological problems. We conducted genome-wide association analyses for cleft palate only (CPO) and cleft lip with or without palate (CL/P) with ~17 million markers in sub-Saharan Africans. After replication and combined analyses, we identified novel loci for CPO at or near genome-wide significance on chromosomes 2 (near CTNNA2) and 19 (near SULT2A1). In situ hybridization of Sult2a1 in mice showed expression of SULT2A1 in mesenchymal cells in palate, palatal rugae and palatal epithelium in the fused palate. The previously reported 8q24 was the most significant locus for CL/P in our study, and we replicated several previously reported loci including PAX7 and VAX1.

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Figures

Figure 1
Figure 1
Manhattan plots of association statistics for CPO (A) and CL/P (B) in sub-Saharan Africa.
Figure 2
Figure 2
(A) Regional association plot in the chromosome 2 locus for CPO. (B) TAD around the chromosome 2 locus for CPO. (C) Ctnna2 expression in mouse embryo at 14.5 days post fertilization (dpf) (Eurexpress–A Transcriptome Atlas of the Mouse Embryo, http://www.eurexpress.org/).
Figure 3
Figure 3
In situ hybridization of Sult2a1 in E12.5 and E14.5 embryos. Blue asterisks show mesenchymal cells in palate; black asterisks, palatal rugae with Sult2a1 expression; red asterisk, palatal epithelium. Tg, tongue; Md, mandible; Mx, maxilla; Ht, heart. Scale bar, 200 μm.
Figure 4
Figure 4
(A) Regional association plot in the chromosome 8q24 locus for CL/P. (B) Haplotype block sizes around the 8q24 lead SNP rs72728755 for CL/P. (C) LD patterns around the 8q24 locus for European (EUR), East Asian (EAS), South Asian (SAS) and continental African (AFR*) ancestries.
Figure 5
Figure 5
(A) Overlay of the three SNPs against chromatin marked as a regulatory element, (B) reporter assay in human fetal oral epithelial cell line (GMSM-K) and (C) primary HEPM.
Figure 6
Figure 6
Haplotype blocks around the lead SNPs from previous GWAS that were replicated in the present study.
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References

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