AUTHOR=Ghazali Norliana , Abd Rahman Normastura , Ahmad Azlina , Sulong Sarina , Kannan Thirumulu Ponnuraj 

TITLE=Identification of Copy Number Variation Among Nonsyndromic Cleft Lip and or Without Cleft Palate With Hypodontia: A Genome-Wide Association Study

JOURNAL=Frontiers in Physiology

VOLUME=12

YEAR=2021

URL=https://www.frontiersin.org/journals/physiology/articles/10.3389/fphys.2021.637306

DOI=10.3389/fphys.2021.637306

ISSN=1664-042X

ABSTRACT=<p>Nonsyndromic cleft lip and or without cleft palate (NSCL/P) with the hypodontia is a common developmental abnormality in humans and animals. This study identified the genetic aberration involved in both NSCL/P and hypodontia pathogenesis. A cross-sectional study using genome-wide study copy number variation-targeted CytoScan 750K array carried out on salivary samples from 61 NSCL/P and 20 noncleft with and without hypodontia Malay subjects aged 7–13 years old. Copy number variations (CNVs) of <italic>SKI</italic> and fragile histidine triad (<italic>FHIT</italic>) were identified in NSCL/P and noncleft children using quantitative polymerase chain reaction (qPCR) as a validation analysis. Copy number calculated (CNC) for each gene determined with Applied Biosystems CopyCaller Software v2.0. The six significant CNVs included gains (12q14.3, 15q26.3, 1p36.32, and 1p36.33) and losses (3p14.2 and 4q13.2) in NSCL/P with hypodontia patients compared with the NSCL/P only. The genes located in these regions encoded <italic>LEMD3</italic>, <italic>IGF1R</italic>, <italic>TP73</italic>, <italic>SKI</italic>, <italic>FHIT</italic>, and <italic>UGT2β15</italic>. There were a significant gain and loss of both <italic>SKI</italic> and <italic>FHIT</italic> copy number in NSCL/P with hypodontia compared with the noncleft group (<italic>p</italic> &lt; 0.05). The results supported that CNVs significantly furnish to the development of NSCL/P with hypodontia.</p>