title: Tracing disease gene(s) in non-syndromic clefts of orofacial region: HLA haplotypic linkage by analyzing the microsatellite markers: MIB, C1_2_5, C1_4_1, and C1_2_A.
abstract: BACKGROUND
  Cleft lip with or without cleft palate (CL/P) is the most frequent craniofacial malformation seen in man. The etiology of CL/P is complex involving both genetic and epigenetic (environmental) factors, and the genes play an almost deterministic role in the normal development of craniofacial structures. This study was aimed at ascertaining the association of HLA microsatellites in CL/P patients.
  
  
  METHODS
  Case DNA was obtained from 76 patients (40M and 36 F, average age 7.8 years, range 1-16 years). Unaffected individuals from the same geographical area without population mixing included as controls (n=154, 76 M and 78 F, average age 8.2 years, range 2-17 years). All DNA samples were purified from peripheral blood by standard techniques.
  
  
  RESULTS
  Four microsatellites were compared in this case-control study. C1_2_5 locus was the most polymorphic marker with 15 observed alleles while C1_4_1 had the least number of alleles. Three of the four markers viz MIB,C1_4_1 and C1_2_5 showed a significant association of microsatellite alleles with CL/P. Five alleles (MIB_326,332,350; C1_4_1 - 213 and C1_2_5-204) were seen with an increased frequency among the test samples, whereas two alleles (C1-4_1_217, and C1_2_5_196) had an increased frequency among the control samples. One allele (C1-4-1-209) had an increased frequency in patient group but was not observed in the controls.
  
  
  CONCLUSIONS
  The role of HLA complex in the pathogenesis of CL/P is speculative and has not been established so far. The result of this study shows that a few alleles have an increased frequency of expression in the diseased group which suggests that these alleles may predispose the individuals to clefting. This finding may be beneficial to aid in early diagnosis and plan intervention strategies.
authors.affiliation: Department of Oral Medicine and Diagnostic Science, College of Dentistry, King Saud University, Post Box: 60169, Riyadh-11545, Kingdom of Saudi Arabia.
authors.forename: R
authors.initials: R
authors.lastname: Rajendran
authors.forename: Saleem F
authors.initials: SF
authors.lastname: Shaikh
authors.forename: Sukumaran
authors.initials: S
authors.lastname: Anil