Mapping of genes involved in cleft lip with or without cleft palate

Candidate genes for CL/P were selected on the basis of involvement in cytogenetic alterations, from published linkage and association studies, and from regions linked to syndromes within which clefting occurs. Linkage analyses were carried out with 8 families with an apparent autosomal dominant inheritance of non-syndromic CL/P, while the association analyses involved 57 unrelated British Caucasian individuals with CL/P and 60 controls. Linkage was excluded between markers D1S65 and D1S58 (lq31), thought to flank the Van der Woude syndrome locus, and the families with CL/P. Multipoint analysis excluded linkage between CL/P and the 2 loci with a maximum lod score of z=-4.0. An association between an RFLP at TGFA (2p13) was confirmed (X2=15.04, p0.5). FISH analysis using two cosmids identified by VIM in a cosmid library screen, did not reveal if VIM was involved in a 10p13 translocation breakpoint in an individual with CL/P. There was no association between KARA (17q21) and unrelated clefted individuals (X2=0.954, p>0.1). Linkage also excluded RARA from a role in familial clefting (z=-3.211, Θ=0.001). In addition to this work, a linkage analysis was carried out between COL2A1 and 6 families with an autosomal dominant inheritance of Stickler syndrome. A maximum lod score of z=0.96, Θ=0.100 was suggestive of either genetic heterogeneity or the involvement of a locus closely linked to COL2A1

The collation of forensic DNA case data into a multidimensional intelligence database

The primary aim of any DNA Database is to link individuals to unsolved offences and unsolved offences to each other via DNA profiling. This aim has been successfully realised during the operation of the New Zealand (NZ) DNA Databank over the past five years. The DNA Intelligence Project (DIP), a collaborative project involving NZ forensic and law enforcement agencies, interrogated the forensic case data held on the NZ DNA Databank and collated it into a functional intelligence database. This database has been used to identify significant trends which direct Police and forensic personnel towards the most appropriate use of DNA technology. Intelligence is being provided in areas such as the level of usage of DNA techniques in criminal investigations, the relative success of crime scene samples and the geographical distribution of crimes. The DIP has broadened the dimensions of the information offered through the NZ DNA Databank and has furthered the understanding and investigative capability of both Police and forensic scientists. The outcomes of this research fit soundly with the current policies of 'intelligence led policing', which are being adopted by Police jurisdictions locally and overseas

Prediction of liability to orofacial clefting using genetic and craniofacial data from parents.

BACKGROUND: Cleft lip with or without cleft palate (CL(P)) and isolated cleft palate (CP) are separate clinical entities and for both polygenic multifactorial aetiology has been proposed. Parents of children with orofacial clefting have been shown to have distinctive differences in their facial shape when compared to matched controls. OBJECTIVE: To test the hypothesis that genetic and morphometric factors predispose to orofacial clefting and that these markers differ for CL(P) and CP. Methods-Polymorphisms at the transforming growth factor alpha (TGFalpha) locus in 83 parents of children with nonsyndromic orofacial clefts were analysed, and their craniofacial morphology was assessed using lateral cephalometry. RESULTS: Parents of children with CL(P) and CP showed an increased frequency of the TGFalpha/TaqI C2 allele (RR=4.10, p=0.009) relative to the comparison group. Also the TGFalpha/BamHI A1 allele was more prevalent in the CP parents. MULTIVARIATE STATISTICAL ANALYSIS: Using stepwise logistic regression analysis the TGFalpha/TaqI C2 polymorphism provides the best model for liability to orofacial clefting. To determine the type of clefting a model involving interaction between the parental TGFalpha/BamHI and TGFalpha/RsaI genotypes showed the best fit. Using genotype only to predict the clefting defect in the children according to parental genotype, 68.3% could be correctly classified. By adding information on craniofacial measurements in the parents, 76% of CP and 94% of CL(P) parents could be correctly classified. CONCLUSIONS: This study provides a model for prediction of liability to orofacial clefting. These findings suggest that different molecular aberrations at the TGFalpha locus may modify the risk for CP and CL(P)