Chromosome 1q21 contains genes linked to psoriasis vulgaris in Chinese Han population / 中华皮肤科杂志

Objective To study the responsible genes of psoriasis vulgaris on chromosome 1q21 in Chinese Han population.Methods Thirty-six families with psoriasis vulgaris,including 92 patients and 98 normal relatives,aged from 12 to 81 years with an average age at 44 years,were enrolled in this study.Blood samples were obtained from all the participants and subjected to DNA extraction.A genome scan was performed with eight microsatellites distributing over chromosome 1q21-1q23.1.Evidence for linkage disequilibrium was assessed with extended transmission disequilibrium test(ETDT)program and Genehunter software.Results Three short tandem repeat markers were found to be associated with psoriasis vulgaris.With Genehunter,evidence for linkage disequilibrium between D1S2345 and psoriasis was found with the NPL value being 1.735(P=0.0329).Moreover,ETDT revealed that the 97-bp allele of D1S2346 and 283-bp allele of D1S484 were preferentially delivered to affected descendants(P＜0.05).Conclusion Chromosome 1q21 contains genes associated with psoriasis vulgaris in Chinese Han population.

Identification of Hereditary Symmetrical Dyschromatosis Susceptibility Locus by Genome-wide Scan / 中华皮肤科杂志

Objective To identify a locus for hereditary symmetrical dyschromatosis(HSD).Methods A genome-wide scan was performed with402microsatellite markers in two large Chinese HSD families to map the chromosome location of the susceptible gene.The LINKAGE software(Version5.10)and CYRILLIC soft-ware(Version2.01)were used for linkage and haplotype analysis.Results A locus was identified at chro-mosome1q11-1q21with a cumulative maximum two-point LOD score of8.85at microsatellite marker D1S2343(?=0.00).Haplotype analysis indicated that the candidate gene was located within11.6cM region between markers D1S2696and D1S2635.This was the first locus identified for HSD.This study provided a map location for isolation of the candidate genes causing HSD.Conclusion Chromosome1q11-1q21contains the candidate gene susceptible for dyschromatosis symmetrica hereditaria.

Linkage analysis of a region on chromosome 2 with essential hypertension in Chinese families / 中华医学杂志(英文版)

<p><b>OBJECTIVE</b>To verify the linkage of the candidate regions identified in a previous study (markers D2S168, D2S151, D2S142 on chromosome 2) with hypertension in Chinese families.</p><p><b>METHODS</b>A genetic linkage study focused on chromosome 2 was performed on 240 Chinese families containing 856 patients with essential hypertension. A total of 1080 individuals were genotyped using 9 highly polymorphic microsatellite markers around the candidate regions on chromosome 2 with an average spacing of 5 cM. Non-parametric linkage (NPL), parametric linkage analysis and transmission-disequilibrium test (TDT) with the GENEHUNTER software were used to assess evidence for linkage.</p><p><b>RESULTS</b>Linkage of a region on chromosome 2 around D2S151 and D2S142 with hypertension was confirmed by different statistical methods (NPL, LOD score and TDT). However, the linkage of D2S168 could not be replicated in this extension study.</p><p><b>CONCLUSIONS</b>The data suggest that a region on chromosome 2 at or near the loci of D2S142 and D2S151 may harbor genes responsible for the development of essential hypertension in Chinese.</p>

Construction and tumorigenic study on a novel fusion gene AML1-MTG16 / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To test whether splicing overlapping extension(SOE) method can be a tool for obtaining rare fusion gene's transcripts and to study the tumorigenic capacity of a novel fusion gene AML1-MTG16.</p><p><b>METHODS</b>SOE method was used to obtain AML1- MTG16 fusion gene's transcripts. MTG16, AML1-MTG16 and AML1-MTG16 without III,VI conserved domains of MTG16 segment were inserted into pEGFP- C1,pDsRed-N1 vector respectively,then transfected NIH3T3 cell line by lipofection. Forty-eight hours later, the transfected cells were examined by laser-scanning confocal microscopy. Stable transfected cells were obtained by G418 500ug/ul selection for one month. Growth curve, soft agar colonies formation tumorigenesis in nude mice were done to compare the difference between stable transfected cells.</p><p><b>RESULTS</b>Recombined AML1-MTG16 by SOE contained its CDS. NIH3T3 expressing AML1-MTG16 had a faster proliferation in medium, colony growth in soft agar. AML1-MTG16 expression cells also induced tumors formation following injection into nude mouse. MTG16,AML1-MTG16 and AML1-MTG16 without III,VI conserved domains of MTG16 were colocalized in the nucleus of cotransfected NIH3T3 cells under the examination of laser-scanning confocal microscope.</p><p><b>CONCLUSION</b>SOE is an effective method to get rare fusion gene's transcripts. AML1-MTG16 plays an important role in leukemogenesis. MTG16 may also have a carcinogenic property within the AML1-MTG16 fusion gene. Carcinogenic property of AML1-MTG16 is restricted to its localization in the nuclear matrix. N terminal of MTG16 may play an important part in the carcinogenic activity of AML1-MTG16.</p>

ER-?gene polymorphisms and the risk of non-BRCA1/2 hereditary breast cancer / 中国普通外科杂志

Objective The present study was to explore association of PvuⅡand XbaⅠpolymorphism in ER-?gene with genetic susceptibility for breast cancer without BRCAl/2 gene mutation. Methods 113 BRCA1/2 negative hereditary breast cancer patients from independent families and 113 agematched healthy control subjects were analyzed. Genotype analysis was conducted by polymerase chain reaction (PCR) and then DNA direct sequencing. The odd-ratios (OR) and 95% confidence intervals (CI) was calculated by unconditional logistic regression model. Results The frequency of PvuⅡpolymorphism CC(PP) ,CT(Pp) ,TT(pp) genotype in patients was found in 16 cases(14.2% ), 58 cases(51. 3% ) , and 39 cases (34. 5% ). The distribution of AA (xx) , AG (Xx) , GG (XX) genotype of XbaⅠpolymorphism were found in 76 cases ( 67. 2% ) , 34 cases ( 30. 1% ), and 3 cases ( 2. 7% ) among patients. Among premenopausal women, CT genotype of PvuⅡconfered a significantly increased risk for breast cancer compared with CC genotype ( adjusted OR = 2. 07; 95% CI, 0. 68 - 6. 30) ; Carriers of GG of XbaⅠhad a decreased risk for breast cancer (adjusted OR =0. 11; 95 % CI, 0. 01 - 1. 27) compared with AA genotype. Furthermore, combined analysis of two polymorphisms indicated individuals carrying PvuⅡCT and XbaⅠAA genotype were at increased risk for breast cancer as compared with those with PvuⅡCC and XbaⅠGG genotype (Oft = 11.43, 95% CI, 1.12-116.7) among premenopausal women. Conclusions PvuⅡand XbaⅠpolymorphisms in ER-?gene could be a candidate locus for low penetrance breast cancer susceptibility in Chinese population, especially among premenopausal women.

The Association of SPRR2E Encoding Sequence Polymorphism and Psoriasis Vulgaris / 中华皮肤科杂志

Objective To investigate the association of SPRR2E gene and psoriasis vulgaris by sequencing the DNA of Chinese Han psoriatic families. Methods DNA was extracted from the peripheral blood cells of thirty-two Chinese psoriatic families. The sequence of the SPRR2E encoding region was measured by ABI377 DNA Sequencer. The linkage disequilibrium was assessed by extended transmission disequilibrium test (ETDT) and GENEHUNTER software. Results An A/G polymorphism at nucleotide 156 of the SPRR2E encoding region was identified. There were three genotypes, including AA, GG and AG. Although the single nucleotide polymorphism (SNP) did not change the encoding of amino acid, the single nucleotide polymorphism locus was associated with psoriasis vulgaris by the ETDT analyzing. The A-allele was found to be transmitted more frequently than that of the G-allele. GENEHUNTER analysis was concordant with the results of the ETDT. Conclusion A single nucleotide polymorphism (SNP) in SPRR2E gene encoding region is associated with psoriasis vulgaris in Han Chinese population.