Biomedical subjects

G M Vintiner

Publications and source records attributed to G M Vintiner.

8 recordsLinked to original sources

PubMed1998

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).

Alleles↗

PubMed1994

Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate.

The inheritance of alleles of the transforming growth factor alpha (TGFA) locus has been studied in families affected with cleft lip with or without cleft palate (CL/P), by using the transmission/disequilibrium test described by Spielman and colleagues. Only heterozygous parents with an affected child can be included in this test, but within such families a significantly greater frequency of C2 alleles were transmitted to affected children than would be expected by chance. There was no evidence that the total number of C2 alleles transmitted to affected and unaffected children differed significantly from random segregation. These data provide evidence from within families that a gene for susceptibility to CL/P is in significant linkage disequilibrium with the C2 allele of the TGFA locus.

Alleles↗

PubMed1993

Exclusion of candidate genes from a role in cleft lip with or without cleft palate: linkage and association studies.

Candidate genes and marker loci for cleft lip/palate (CL/P) were tested using linkage analyses and association studies. Eight British families with apparent autosomal dominant inheritance of non-syndromic CL/P participated in the linkage analyses while the association analyses involved 61 unrelated British white people with CL/P and 60 controls. The report of an association between RARA (17q21) and unrelated Australian persons with CL/P (p = 0.016) was not confirmed in British CL/P persons (chi 2 = 0.954, p > 0.1). There was also no evidence of linkage between RARA and the eight CL/P families (Z = -3.211, theta = 0.001). Linkage was excluded between familial CL/P and F13A1 (map position 6p24-25) with an observed maximum lod score of Z = -2.052 at theta = 0.05. No association was found between alleles at VIM (10p13) and the British CL/P subjects (chi 2 = 0.110, p > 0.5). Multipoint analysis excluded linkage between familial CL/P and the markers D1S65 and D1S58 which flank the Van der Woude syndrome locus with a maximum lod score of Z = -4.0. This suggests that the genetic defect underlying VWS is not the same as in non-syndromic CL/P. There was no evidence of linkage between CRTL1 (5q15) and the eight CL/P families (Z = -3.466, theta = 0.05).

Base Sequence↗

PubMed1992

Confirmation of an association between RFLPs at the transforming growth factor-alpha locus and non-syndromic cleft lip and palate.

Three RFLPs at the TGFA locus were studied in 60 unrelated British Caucasian subjects with non-syndromic cleft lip/palate and 60 controls. A highly significant association between the TaqI RFLP and the occurrence of clefting was found (chi 2 = 15.04, p = less than 0.001). No significant association was found with the two other RFLPs studied (BamHI and RsaI). Haplotypes derived from the three RFLPs at the TGFA locus also showed an over-representation of the C2A2B2 haplotype in cases compared to controls. Analyses of genotypes according to type of cleft and the presence or absence of a family history of clefting were also carried out. These results provide further support for the role of TGFA as a gene of major effect in the development of orofacial clefts in humans.

Alleles↗

PubMed1992

No evidence of linkage between the transforming growth factor-alpha gene in families with apparently autosomal dominant inheritance of cleft lip and palate.

Eight families have been identified with cleft lip, with or without cleft palate (CL/P), inherited in an apparently autosomal dominant manner. Transforming growth factor-alpha (TGFA) has been tested as a candidate gene for clefting in these families. Negative lod scores were generated in an autosomal dominant model with 80% penetrance (Z = -3.152 at theta = 0.05 and Z = -2.49 at theta = 0.05 with only affected subjects scored). After testing with a reduced penetrance of 28%, less negative lod scores were generated (Z = -0.157 at theta = 0.00), but there was still no evidence of linkage. An autosomal recessive model with a penetrance of 35% was also tested. Regardless of the model used there was little evidence of linkage between TGFA and the CL/P phenotype, which is in contrast to the previously published findings of an association between TGFA and CL/P in unrelated subjects.

Cleft Lip↗

PubMed1991

Genetic and clinical heterogeneity of Stickler syndrome.

We have studied 6 multigeneration Stickler syndrome families. Manifestations of the syndrome in the families included myopia, deafness, arthritis, characteristic facial changes with "flat" midface and cleft palate, although not all these were present in all families. COL2A1 has been implicated as a gene which can give rise to Stickler syndrome based on evidence from 2 large families which each showed significant linkage between the disease locus and restriction fragment length polymorphisms for the gene (Francomano CA, Lieberfarb RM, Hirose T, Maumenee IH, Streeten EA, Meyers DA, Pyeritz RE (1987): Genomics 1:293-296; Knowlton RG, Weaver EJ, Struyk AF, Knobloch WH, King RA, Norris K, Shamban A, Uitoo J, Jimenez SA, Prockop DJ (1989): Am J Hum Genet 45:681-688). We have found crossovers between the disease locus and COL2A1 in 2 families with Stickler syndrome. This could be explained by either genetic heterogeneity or the actual mutation being in a closely linked, currently unrecognized gene. We found a weakly positive overall lod score (z = 0.96 at theta = 0.10) suggesting that genetic heterogeneity is a more likely explanation. In one family, with typical findings, a translocation t5;17 (q15:q23) was found to segregate with the disease in 4 affected relatives. In view of the possible heterogeneity, although no crossovers with COL2A1 were seen in this family, either of these breakpoints could be the position of a further disease causing gene.

Abnormalities, Multiple↗

PubMed1990

Effect of monofluorophosphate on calcium phosphate formation in supersaturated solutions.

The effect of purified monofluorophosphate (MFP) on the formation of hydroxyapatite (HA) in supersaturated calcium phosphate solutions was determined. In solutions initially at pH 7.4 and seeded with HA crystals, MFP was hydrolysed to a small extent, releasing F-. Once the crystal growth-enhancing property of this F- was compensated for, 4 mmol/l MFP could be shown to inhibit precipitation by 40%. Without compensation for F-, MFP appeared to inhibit precipitation by only 18%. This inhibition was weaker than that caused by pyrophosphate or ethane-1-hydroxy-1,1-diphosphonic acid. Because MFP is hydrolysed on apatite surfaces to F-, use of sodium MFP as an anticaries agent is unlikely to cause significant inhibition of enamel remineralization.

Calcium↗

PubMedDate not supplied

The collation of forensic DNA case data into a multi-dimensional intelligence database.

The primary aim of any DNA Database is to link individuals to unsolved offenses and unsolved offenses 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 investigation, 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.

Databases, Nucleic Acid↗