[Analysis on genetic polymorphism of 5 STR loci selected from X chromosome].

OBJECTIVE: To select short tandem repeats(STR) from X chromosome. METHODS: STR is a universal genetic marker that has changeable polymorphism and stable heredity in human genome. It is a specific DNA segment composed of 2-6 base pairs as its core sequence. It is an ideal DNA marker used in linkage analysis and gene mapping. In this study, 8 short tandem repeats were selected from two genomic clones on X chromosome by using BCM Search Launcher. Primers amplifying the STR loci were designed by using Primer 3.0 according to the unique sequence flanking the STRs. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. RESULTS: Five of these STRs were polymorphic. Chi-square test indicated that the distribution of genotypes agreed with Hardy-Weinberg equilibrium (P>0.05). CONCLUSION: Five polymorphic short tandem repeats have been identified on chromosome X and will be useful for linkage analysis and gene mapping.

[The "horse-shoe effect"of correspondence analysis for human population genetic structure and its population genetic explanation].

At present study, the reasons of "horse-shoe effect" in correspondence analysis for analyzing human population genetic structure was explained. Based on the structure of gene frequency matrix, we displaye the different patterns of Scallergram of correspondent analysis from different types of loci (HLA-A locus, and STR- CSF1PO locus in Chinese Han populations). The results indicate that different types of loci showed different patterns of Scallergram of correspondent analysis. When some alleles have very low frequency in the gene frequency matrix, there would be "horse-shoe effect" in the Scallergram of correspondent analysis. The reason is that the c2 distance measurement in correspondent analysis usually overrates the effect of the genes with low frequencies. To carry out the correspondent analysis of human population genetic structure, when the Scallergram presents "horse-shoe effect", one should examine the structure of gene frequency matrix, and confirm whether the "horse-shoe effect" shows the real pattern of population genetic structure. Only in this way, one can explain the "horse-shoe effect" correctly.

[Characterization of genomic structure and mutation analysis of SMARCA1 gene in a Smith-Fineman-Myers syndrome family].

The study is to determine the genomic structure and the role of SMARCA1 (SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily A, member1, SMARCA1) in the etiology of Smith-Fineman-Myers syndrome (SFMS). By comparing the cDNA sequence of SMARCA1 with the genomic sequences, genomic structure of SMARCA1 was determined, and conformed by amplifying and sequencing the sequences of exons and splicing junction. The results show that the genomic sequence of SMARCA1 gene exceeds 71.7 kb in length, and contains 24 exons and 23 introns. All the exon/intron boundaries follow the GT-AG rule and are in good agreement with the exon/intron consensus sequence. The characterization of genomic structure of SMARCA1 gene allows us to detect disease-causing mutation within the gene and further study its biological function. The open reading frame of SMARCA1 was detected for mutation by PCR amplification and direct sequencing in affected males from SFMS family in Shandong China. The disease in SFMS family from Shandong is not caused by the mutation within open reading frame of SMARCA1 gene.

[Multiple nonlinear statistical method of population genetic structure based on the allelic polymorphism data].

The distribution and structure of the allelic polymorphism data are analyzed and it is pointed out that the distribution of allelic polymorphism data reveals the characteristic of closed data (also named as compositional data or data of constant sum). It is interpreted that the correlation structure of the allelic polymorphism data contains null correlations introduced by "closure" and the statistical distribution of the data is not normal because of its constant row sum, which resulted in great difficulties in analyzing the data with traditional multiple linear statistical methods such as principal component analysis, factor analysis, cluster analysis and canonical correlation analysis. Based on the theory of compositional data analysis proposed by Aitchison in 1982, a multiple nonlinear statistical method originating from the "logratios" approach to the statistical analysis of compositional data is put forward in this paper. As an example, the "logratios" method was used to analyze the genetic structure of TH01 polymorphic loci in Chinese population and the results were compared with those of multiple linear methods such as component principal. It is concluded that the "logratios" multiple nonlinear principle component analysis is a better method with the virtue of sensitivity and specificity for analyzing the genetic structure of population from the data of allelic polymorphism.

[Polymorphic loci and polymorphism analysis of short tandem repeats within XNP gene].

To select polymorphic short tandem repeat markers within X-linked nuclear protein (XNP) gene, genomic clones which contain XNP gene were recognized by homologous analysis with XNP cDNA. By comparing the cDNA with genomic DNA, non-exonic sequences were identified, and short tandem repeats were selected from non-exonic sequences by using BCM search Launcher. Polymorphisms of the short tandem repeats in Chinese population were evaluated by PCR amplification and PAGE. Five short tandem repeats were identified from XNP gene, two of which were polymorphic. Four and 11 alleles were observed in Chinese population for XNPSTR1 and XNPSTR4, respectively. Heterozygosities were 47% for XNPSTR1 and 70% for XNPSTR4. XNPSTR1 and XNPSTR4 localized within 3' end and intron 10, respectively. Two polymorphic short tandem repeats have been identified within XNP gene and will be useful for linkage analysis and gene diagnosis of XNP gene.

[Fine mapping of Smith-Fineman-Myers syndrome and exclusion of GPC3, GPCR2 MST4 and GLUD2 as candidate genes].

OBJECTIVE: Smith-Fineman-Myers syndrome (SFMS) is an X-linked mental retardation syndrome. The authors had ascertained a large Chinese family with SFMS from Shandong and had mapped the disease locus to an interval of 19.8 Mb on Xq25 flanked by markers DXS8064 and DXS8050. Further investigation suggested that SFMS exhibited locus heterogeneity. In this study for facilitating the identification of the gene responsible for SFMS, the additional markers were analyzed to narrow down the candidate region, and four candidate genes (GPC3, MST4,GPCR2 and GLUD2) were chosen and screened for disease-causing mutation. METHODS: PCR and denaturing polyacrylamide gel electrophoresis were used to genotype 13 new polymorphic markers distributed within the candidate region. Mutation detection was accomplished by sequencing the exons and intron-exon junctions of the candidate genes. RESULTS: By analyzing 13 additional polymorphic markers, SFMS candidate region can be reduced to an interval of 10.18 Mb bounded by XSTR3 and XSTR4, and no disease-causing mutation was identified in the coding regions of four candidate genes. CONCLUSION: GPCR2 GPC3, MST4 and GLUD2 were excluded as pathogenic genes for SFMS. The refined SFMS locus will assist in the identification and characterization of other candidate genes for SFMS.