title: Discovery of candidate genes for nonsyndromic cleft lip palate through genome-wide linkage analysis of large extended families in the Malay population.
abstract: BACKGROUND
  Nonsyndromic orofacial clefts are one of the most common birth defects worldwide. It occurs as a result of genetic or environmental factors. This study investigates the genetic contribution to nonsyndromic cleft lip and/or palate through the analysis of family pedigrees. Candidate genes associated with the condition were identified from large extended families from the Malay population.
  
  
  RESULTS
  A significant nonparametric linkage (NPL) score was detected in family 100. Other suggestive NPL and logarithm of the odds (LOD) scores were attained from families 50, 58, 99 and 100 under autosomal recessive mode. Heterogeneity LOD (HLOD) score ≥ 1 was determined for all families, confirming genetic heterogeneity of the population and indicating that a proportion of families might be linked to each other. Several candidate genes in linkage intervals were determined; LPHN2 at 1p31, SATB2 at 2q33.1-q35, PVRL3 at 3q13.3, COL21A1 at 6p12.1, FOXP2 at 7q22.3-q33, FOXG1 and HECTD1 at 14q12 and TOX3 at 16q12.1.
  
  
  CONCLUSIONS
  We have identified several novel and known candidate genes for nonsyndromic cleft lip and/or palate through genome-wide linkage analysis. Further analysis of the involvement of these genes in the condition will shed light on the disease mechanism. Comprehensive genetic testing of the candidate genes is warranted.
authors: Reconstructive Science Unit, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. sya_escoe@yahoo.co.uk.
authors: Nurul Syazana
authors: NS
authors: Mohamad Shah
authors: Department of Biology, School of Basic Sciences, Science and Research Branch, Islamic Azad University, Isfahan, Iran. isalahshouri@gmail.com.
authors: Iman
authors: I
authors: Salahshourifar
authors: Human Genome Center, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. ssarina@usm.my.
authors: Sarina
authors: S
authors: Sulong
authors: Reconstructive Science Unit, School of Medical Sciences, Universiti Sains Malaysia, Kelantan, Malaysia. wazman@usm.my.
authors: Wan Azman
authors: WA
authors: Wan Sulaiman
authors: School of Medical Sciences, Health Campus, Universiti Sains Malaysia, Kelantan, Malaysia. ashalim@usm.my.
authors: Ahmad Sukari
authors: AS
authors: Halim
mesh_terms: D051017:Apoptosis Regulatory Proteins; D044466:Asian People / Q000235:genetics*; D001921:Brain / Q000002:abnormalities*; D015815:Cell Adhesion Molecules / Q000235:genetics; D002874:Chromosome Mapping; D002971:Cleft Lip / Q000175:diagnosis* / Q000235:genetics*; D002972:Cleft Palate / Q000175:diagnosis* / Q000235:genetics*; D030541:Databases, Genetic; D051858:Forkhead Transcription Factors / Q000235:genetics; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006609:High Mobility Group Proteins; D006801:Humans; D008126:Lod Score; D008296:Malaysia; D036961:Matrix Attachment Region Binding Proteins / Q000235:genetics; D046228:Microarray Analysis; D000075983:Nectins; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D043562:Receptors, G-Protein-Coupled / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics; D044767:Ubiquitin-Protein Ligases / Q000235:genetics
chemical_list: D051017:Apoptosis Regulatory Proteins; D015815:Cell Adhesion Molecules; D051858:Forkhead Transcription Factors; D006609:High Mobility Group Proteins; D036961:Matrix Attachment Region Binding Proteins; D000075983:Nectins; D043562:Receptors, G-Protein-Coupled; D011980:Receptors, Progesterone; D015534:Trans-Activators; D014157:Transcription Factors; D044767:Ubiquitin-Protein Ligases; C117618:ADGRL2 protein, human; C465448:FOXP2 protein, human; C000619014:NECTIN3 protein, human; C521297:SATB2 protein, human; C521752:TOX3 protein, human; C000588989:HECTD1 protein, human