{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T22:01:17Z","timestamp":1783720877974,"version":"3.55.0"},"reference-count":99,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2023,3,7]],"date-time":"2023-03-07T00:00:00Z","timestamp":1678147200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Orofacial clefts (OFCs) are common congenital disabilities that can occur as isolated non-syndromic events or as part of Mendelian syndromes. OFC risk factors vary due to differences in regional environmental exposures, genetic variants, and ethnicities. In recent years, significant progress has been made in understanding OFCs, due to advances in sequencing and genotyping technologies. Despite these advances, very little is known about the genetic interplay in the Malagasy population. Methods: Here, we performed high-resolution whole-exome sequencing (WES) on non-syndromic cleft lip with or without palate (nCL\/P) trios in the Malagasy population (78 individuals from 26 families (trios)). To integrate the impact of genetic ancestry admixture, we computed both global and local ancestries. Results: Participants demonstrated a high percentage of both African and Asian admixture. We identified damaging variants in primary cilium-mediated pathway genes WNT5B (one family), GPC4 (one family), co-occurrence in MSX1 (five families), WDR11 (one family), and tubulin stabilizer SEPTIN9 (one family). Furthermore, we identified an autosomal homozygous damaging variant in PHGDH (one family) gene that may impact metabiotic activity. Lastly, all variants were predicted to reside on local Asian genetic ancestry admixed alleles. Conclusion: Our results from examining the Malagasy genome provide limited support for the hypothesis that germline variants in primary cilia may be risk factors for nCL\/P, and outline the importance of integrating local ancestry components better to understand the multi-ethnic impact on nCL\/P.<\/jats:p>","DOI":"10.3390\/genes14030665","type":"journal-article","created":{"date-parts":[[2023,3,8]],"date-time":"2023-03-08T03:29:05Z","timestamp":1678246145000},"page":"665","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Genome Analysis Using Whole-Exome Sequencing of Non-Syndromic Cleft Lip and\/or Palate from Malagasy Trios Identifies Variants Associated with Cilium-Related Pathways and Asian Genetic Ancestry"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9705-4088","authenticated-orcid":false,"given":"Zarko","family":"Manojlovic","sequence":"first","affiliation":[{"name":"Department of Urology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"},{"name":"Department of Translational Genomics, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allyn","family":"Auslander","sequence":"additional","affiliation":[{"name":"Operation Smile Inc., Virginia Beach, VA 23453, USA"},{"name":"Division of Plastic and Maxillofacial Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, CA 90027, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxin","family":"Jin","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8789-9917","authenticated-orcid":false,"given":"Ryan J.","family":"Schmidt","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine, Children\u2019s Hospital Los Angeles, Los Angeles, CA 90027, USA"},{"name":"Department of Pathology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8508-4706","authenticated-orcid":false,"given":"Yili","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sharon","family":"Chang","sequence":"additional","affiliation":[{"name":"Department of Translational Genomics, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruocen","family":"Song","sequence":"additional","affiliation":[{"name":"Department of Urology, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sue A.","family":"Ingles","sequence":"additional","affiliation":[{"name":"Department of Population and Public Health Sciences, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alana","family":"Nunes","sequence":"additional","affiliation":[{"name":"Agilent Technologies, Inc., Santa Clara, CA 95051, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8723-0401","authenticated-orcid":false,"given":"KC","family":"Vavra","sequence":"additional","affiliation":[{"name":"Agilent Technologies, Inc., Santa Clara, CA 95051, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Devin","family":"Feigelson","sequence":"additional","affiliation":[{"name":"Operation Smile Inc., Virginia Beach, VA 23453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvia","family":"Rakotoarison","sequence":"additional","affiliation":[{"name":"Operation Smile Madagascar, Antananarivo 105, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Melissa","family":"DiBona","sequence":"additional","affiliation":[{"name":"Operation Smile Inc., Virginia Beach, VA 23453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathy","family":"Magee","sequence":"additional","affiliation":[{"name":"Operation Smile Inc., Virginia Beach, VA 23453, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Operation","family":"Smile","sequence":"additional","affiliation":[{"name":"Operation Smile Inc., Virginia Beach, VA 23453, USA"},{"name":"Operation Smile Madagascar, Antananarivo 105, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anjaramamy","family":"Ramamonjisoa","sequence":"additional","affiliation":[{"name":"Operation Smile Madagascar, Antananarivo 105, Madagascar"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William","family":"Magee III","sequence":"additional","affiliation":[{"name":"Operation Smile Inc., Virginia Beach, VA 23453, USA"},{"name":"Division of Plastic and Maxillofacial Surgery, Children\u2019s Hospital Los Angeles, Los Angeles, CA 90027, USA"},{"name":"Division of Plastic and Reconstructive Surgery, Keck School of Medicine of USC, Los Angeles, CA 90033, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1773","DOI":"10.1016\/S0140-6736(09)60695-4","article-title":"Cleft lip and 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