Abstract no. 2184published_or_final_versio

Lok, ASF

Ma, CK

Ng, SW

Tam, SCF

Wong, RMC

The American Journal of Human Genetics

HKU Scholars Hub

TitlePCR amplification of alleles at locus D17S5: population geneticstudy in Hong Kong Chinese and detection of allelic loss inpatients with hepatocellular carcinomaAuthor(s) Ma, CK; Tam, SCF; Ng, SW; Wong, RMC; Lok, ASFCitationThe 46th Annual Meeting of the American Society of HumanGenetics, San Francisco, California, USA; 29 October - 2November 1996, v. 59 n. Suppl, p. A374Issued Date 1996URL http://hdl.handle.net/10722/57553Rights Creative Commons: Attribution 3.0 Hong Kong LicensePublished Abstracts: Genetic Epidemiology and Population Genetics (cont.)2179The strength of linkage disequilibrium between two vitamin D receptorpolymorphisms varies by ethnicity. S. A. Inglesi, R. W. Hlaile', B. E. Henderson',L. N. Kolonel3, G. Nakaichi', G.-Y.Shi,4, M. C. Yu', R. K. Ross', G. A. Coetzee2.Departments of Preventive Medicinel & Urology2, Norris Comprehensive CancerCenter, University of Southern California School of Medicine. 3Cancer Research Centerof Hawaii, IJniversity of llawaii, llonolulu, 4Department of Community, Occupational,and Family Medicine, National University of Singapore.To evaluate the adequacy of a commonly used Bsinl RFLP as a marker of the vitaminD receptor (VDR) locus, we genotyped 583 individuals from 4 ethnic groups for thismarker, as well as for a polymorphic site in the 3' untranslated region (3'UTR) of thisgene. At the latter site, we identified 12 alleles, A13 to A24, of a poly-A microsatellitelocated approximately 1 kb upstream from the 3' end of the 3.2 kb 3'UTR. Allele sizefollowed a bimodal distribution with distinct short (AW3-A,7) and long (Als-A24) allelepopulations. Poly-A allele frequency differed by ethnicity, with the frequency of shortalleles being highest in non-Ilispanic whites (41%), intermediate in African-Americansand Hispanics (29% and 31%, respectively), and lowest in Asians (14%). In each ofthe four ethnic groups, both the Bsml and the poly-A markers were in llardy-Weinbergequilibrium, and some degree of linkage disequilibrium was observed with coupling be-tween 13smil and short poly-A alleles and between BsmI b and long poly-A alleles. Thestrength of the linkage disequilibrium varied by ethnicity, with departures from completedisequilibrium producing disagreement between the BsmI and poly-A genotypes. Geno-typic disagreement was lowest in non-Hispanic whites (7%), intermediate in Asians andHispanics (16% and 19%, respectively), and highest among African Americans (37%),indicating that BsmI is not a good marker for the VDR 3'UTR genotype in all popula-tions.2181Overlapping genetic susceptibilities In IDDM and Cystic FibrosisComplicated by Diabetes (CFIDM): Benefit of dual quantitativeassessments In related diseases. L.J. Krueger'. D.S. Hoisclaw. Jr'. H.L.Dorkin2 and M. Carringtor?. Dept of Pediatrics Med. College of PA &Hahnemann University, Philadelphia, PA; Div. of Pediatric Pulmonology andAllergy2, Tufts University SOM, Boston, MA & Biological Carcinogenesis andDevelopment Program3, National Cancer Institute, FCRDC, Frederick, MD.The incidence of CF complicated by diabetes (CFIDM) is much higherthan that found in Type insulin-dependent diabetes mellitus (IDDM) in thegeneral population (12% versus 0.1%). In our previous study [J. ClinImmunol. 14(6):353-358, 1994J, the incidence DQa and DQ0I genotypes inthe CF/DM population (n=26) were in disequilibrium compared to the normalcontrol and CF/non-DM populations (n=42). In a pt.-matched, totalascertainment study of CF/DM, an increased allele frequency of the Asp57allele, DQB1*0201 was determined (40.4% versus 28.0% for CF/DM andCF/non-DM). The IDDM protective Asp57* alleles were lower in the CF/DMversus CF/non-DM (p c 0.025) or normal controls (p< 0.008). Oneinterpretations of the MHC results underscores a potential mechanisticconflict between CF/DM (a non-autoimmune disorder) and IDDM (anautoimmune disease). By assessing other known diabetogenic loci, thisinterpretation may be tested.However, identifying susceptibility genes in multifactorial diseases isdifficult and even more difficult in CF/DM because of limiting pedigree size.In this ongoing multicenter trial (10 National CF Clinical Centers) of CF/DMusing a matched-design [n=139 CF/DM (1x) and n=?00 CF/non-DM (2X)J,we hope to establish that the investigation of related diseases will not onlyconfirm the identity of candidate IDDM susceptibility genes, but may providefresh insight into the diabetogenic process encoded by these genes.2183A mIinstion of HIA-oQAI owon 52 and HLA-i4 confers susctibility lfo fnsulin-depdent diabetes eellitus. S.P. Lin , Y.J. Lee, F.S. Lo' and J.G. C, . Dept ofPediatrics, Mackay Memorial Hospital, Taipei. and ,Dept of Moecular Modcine. TaipeiMunicipal Jen-Ai Hospital, Taipei, Taiwan.To date, more than twelve separate chromosome regions have been implicated in thedevelopeent of human type I diabetes mellitus (IOOM). A sajor part of the geneticsusceptibility to this disease in husane has been sapped to the husan leukocyte antigen(HLA) class II region (OR, OP. and OQ). We, therefore, analysed the HUA-OQA1 52 andHLA-OR4 between TIOOM children and healthy old control subjects. The method involved theselective amplification of a DNA fragment fro the HLA-OQAl and HLA-OR4 gene by usingthe mutagenic primers. After PCR, we can accurately obtain the results after enzymedigestion and electrophoresis. Sixty-seven IOOM patients and 69 nondiabetic controlsubjects were analysed using this method. Statistical analysis wae evaluated using Xtests with Yates correction when appropriate. About the result, please ee the tables.We concluded that susceptibility is confered by DQAl 52 (Arg) as well as DR4.Individuals with two OQA1 52 (Arg) alleles and CR4 hosozygous or heterozygous did nothave more relative risk for disease. Therefore, OQA1 52 (Arg) and CR4 alleles areindependent risk factors. We suggest that other genes in this region may be responsiblefor the disease.Table 1OQA1 IDOM f Control f RR P CR4 10CM f Control f RR PArg/Arg 53 0.79 24 0.35 7.0 <0.05 o/v;v/- 33(1:32) 0.50 17(3;14) 0.24 3.16 <0.05Arg/- 13 0.19 35 0.51 NS -3-34 0.50 52 0.76 NS-/- 1 0.02 10 0.14 NS Total 67 69Table 2OQA1 52 OR4 IOOM Control RR P(n-67) (n-69)Arg/Arg ./../- 26 11 3.3 <0.05Arg/Arg -/- 27 13 2.9 <0.05Arg/- v/v,./- 7 6 NSArg/- -/- 6 29 NS-/- of. 0 0 MS-/- -/- 1 10 NS2180Consanguinity and common adult diseases in Israel Arabcommunities. L. Jaber2. T. Shohat*. J.I. Rotter andM. Shohat*. *Department of Medical Genetics, Rabin MedicalCenter, Beilinson Campus, Petah Tiqva, 2Taybe Children'sledical Center, Taybe Tel Aviv University, Israel andMedical Genetics and Birth Defect Center, Cedars-SinaiMedical Center and UCLA, Los Angeles, CA, USA.While consanguinity has been proven to have adeleterious effect with regard to congenital malformationand rare autosomal recessive diseases, little informationexists on its role in multifactorial common adultmorbidity. The aim of this study was to investigate theeffects of consanguinity on the prevalence of commondiseases in adulthood such as diabetes mellitus,myocardial infarction, bronchial asthma and duodenalulcer. As part of a larger study aiming to investigate theinbreeding coefficient in the Israeli-Arab community,wedistributed questionnaires to parents of 4100 second-gradestudents in 158 randomly chosen schools. Among the 3772responders (92%), 34.8% of the students' fathers and 31%of their mothers were found to be products of con-sanguineous matings. There was no difference in theprevalence (males, females) between the offspring ofconsanguineous versus non-consanguineous matings fordiabetes mellitus (consanguinity: 4.3%, 1.5% vs non-consanguinity: 2.9%, 1.6%) myocardial infarction (2.7%,0.03% vs 2.3%, 0.03%), bronchial asthma (2.4%, 2.0%, vs3.7%, 2.3%) or duodenal ulcer (7.0%, 3.0% vs 7.8%, 2.9%),respectively.This study suggests that ever in a populationwith a high rate of consanguinity, there is no significantincrease in the prevalence of these common adult diseases.2182Lack of association of CHRNA4 S248F mutation with epilepticsyndromes with presumed genetic etiology. W.L. Lee'. A.H.N. 2P.S. Low3. L.Y. Wong2. H.T. Qng3 and U. Raian4. Tan Tock Seng Hospital1,Institute of Molecular and Cell Biology, National University of Singapore2,National University Hospital3, School Health Services4.A missense mutation in the alpha4 subunit of the nicotinic acetylcholinereceptor (CHRNA4) has been found to be associated with autosomaldominant frontal lobe epilepsy. In addition, a nonsense mutation inCHRNA4 has been reported to cosegregate with 20q-linked benignneonatal familial convulsions.As part of an ongoing evaluation of neurotransmitter mutations in epilepsy,we investigated CHRNA4 as a candidate gene for various forms ofepilepsies which are thought to be genetic in etiology. A total of 101patients with one of the following epileptic syndromes were evaluated:benign focal epilepsy of childhood (31), childhood absence epilepsy (26),juvenile absent epilepsy (2), juvenile myoclonic epilepsy (14),photosensitive epilepsy (7), benign familial infantile epilepsy (5), benignfamilial neonatal convulsions (1), primary generalized epilepsy withgeneralized tonic-clonic seizures (6). Nine patients had idiopathic epilepsy-and strong family history of idiopathic epilepsy.Genomic DNA from lymphocytes was used in a PCR assay (Steinlein etal, 1995) which allowed for rapid detection of the missense mutation thatreplaces serine with phenylalanine at codon 248, a highly conserved aminoacid residue in the second transmembrane domain. All 101 samplesexamined failed to show this mutation.The S248F mutation in CHRNA4 does not appear to be associated withthe idiopathic epileptic syndromes examined in this study.2184PCR Amplification of Alleles at Locus D17S5: Population GeneticStudy in Hong Kong Chinese and Detection of Allelic loss in patientswith Hepatocellular Carcinoma. C.K.Mal, S.C.F.Tam, S.W.Ngs,2 3 1 2R.M.C.Wongg and A.S.F.Lok Dept. of Clinical Biochemistry, VirusUnit, Queen Mary I lospital, I long Kong and Dept. of Internal Medicine,University of Michigan, Ann Arbor, U.S.A.1)17S5, a highly polymorphic, variable number of tandem repeat(VN IR) locus, have proven a powerful tool for paternity testing, geneticdisease mapping. individual identification in forensic science, anddeternmination of clonality in human tumors. A population genetic studywas performed to provide a database for the probability calculation offorensic identification and paternity testing. In addition, the application ofthe 1)17S5 locus in detection of loss of heterozygosity (LOH) inchromosome 17p in hepatocellular carcinoma (HCC) was demonstrated.In the population genetic study, a total of 102 genotypes corresponding to19 alleles were found in a population of 953 Hong Kong Chineseindividuals. The most frequent alleles were, 4>1>5>6. The allelicfrequency were significantly different from the Caucasian populations(p<0.OOI). Thc expected and observed heterozygosity were 89.5% and90.3% respectively. The discrimination power was 0.98. The chance ofexclusion was 0.79. In the LOH study. 46 1ICC patients were studied, 39cases were found informative and 15 have loss ofheterozygosity(38.5%).A374

PCR amplification of alleles at locus D17S5: population genetic study in Hong Kong Chinese and detection of allelic loss in patients with hepatocellular carcinoma

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PCR amplification of alleles at locus D17S5: population genetic study in Hong Kong Chinese and detection of allelic loss in patients with hepatocellular carcinoma

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