title: Genomewide scan for nonsyndromic cleft lip and palate in multigenerational Indian families reveals significant evidence of linkage at 13q33.1-34.
abstract: Nonsyndromic cleft lip with or without cleft palate (CL-P) is a common congenital anomaly with incidence ranging from 1 in 300 to 1 in 2,500 live births. We analyzed two Indian pedigrees (UR017 and UR019) with isolated, nonsyndromic CL-P, in which the anomaly segregates as an autosomal dominant trait. The phenotype was variable, ranging from unilateral to bilateral CL-P. A genomewide linkage scan that used approximately 10,000 SNPs was performed. Nonparametric linkage (NPL) analysis identified 11 genomic regions (NPL>3.5; P<.005) that could potentially harbor CL-P susceptibility variations. Among those, the most significant evidence was for chromosome 13q33.1-34 at marker rs1830756 (NPL=5.57; P=.00024). This was also supported by parametric linkage; MOD score (LOD scores maximized over genetic model parameters) analysis favored an autosomal dominant model. The maximum LOD score was 4.45, and heterogeneity LOD was 4.45 (alpha =100%). Haplotype analysis with informative crossovers enabled the mapping of the CL-P locus to a region of approximately 20.17 cM (7.42 Mb) between SNPs rs951095 and rs726455. Thus, we have identified a novel genomic region on 13q33.1-34 that harbors a high-risk variant for CL-P in these Indian families.
authors.affiliation: Green Cross Blood Bank and Genetic Research Centre, Paldi, India. uppala@medecine.unige.ch
authors.forename: Uppala
authors.initials: U
authors.lastname: Radhakrishna
authors.forename: Uppala
authors.initials: U
authors.lastname: Ratnamala
authors.forename: Mathew
authors.initials: M
authors.lastname: Gaines
authors.forename: Soraya
authors.initials: S
authors.lastname: Beiraghi
authors.forename: David
authors.initials: D
authors.lastname: Hutchings
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Golla
authors.forename: Syed A
authors.initials: SA
authors.lastname: Husain
authors.forename: Prakash S
authors.initials: PS
authors.lastname: Gambhir
authors.forename: Jayesh J
authors.initials: JJ
authors.lastname: Sheth
authors.forename: Frenny J
authors.initials: FJ
authors.lastname: Sheth
authors.forename: Ghati K
authors.initials: GK
authors.lastname: Chetan
authors.forename: Mohammed
authors.initials: M
authors.lastname: Naveed
authors.forename: Jitendra V
authors.initials: JV
authors.lastname: Solanki
authors.forename: Uday C
authors.initials: UC
authors.lastname: Patel
authors.forename: Dilipkumar C
authors.initials: DC
authors.lastname: Master
authors.forename: Rafiq
authors.initials: R
authors.lastname: Memon
authors.forename: Gregory S
authors.initials: GS
authors.lastname: Antonarakis
authors.forename: Stylianos E
authors.initials: SE
authors.lastname: Antonarakis
authors.forename: Swapan K
authors.initials: SK
authors.lastname: Nath
mesh_terms: D002882:Chromosomes, Human, Pair 13 / Q000235:genetics*; D002971:Cleft Lip / Q000235:genetics*; D002972:Cleft Palate / Q000235:genetics*; D008040:Genetic Linkage; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D007194:India; D010375:Pedigree; D020161:Physical Chromosome Mapping