Identification of GLI Mutations in Patients With Hirschsprung Disease That Disrupt Enteric Nervous System Development in Mice.

Background & Aims: Hirschsprung disease is characterized by a deficit in enteric neurons, which are derived from neural crest cells (NCCs). Aberrant hedgehog signaling disrupts NCC differentiation and might cause Hirschsprung disease. We performed genetic analyses to determine whether hedgehog signaling is involved in pathogenesis.

Depletion of the IKBKAP ortholog in zebrafish leads to hirschsprung disease-like phenotype.

Aim: To investigate the role of IKBKAP (inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase complex-associated protein) in the development of enteric nervous system (ENS) and Hirschsprung disease (HSCR).

Methods: In this study, we injected a morpholino that blocked the translation of ikbkap protein to 1-cell stage zebrafish embryos. The phenotype in the ENS was analysed by antibody staining of the pan-neuronal marker HuC/D followed by enteric neuron counting.

A three-stage genome-wide association study combining multilocus test and gene expression analysis for young-onset hypertension in Taiwan Han Chinese.

Background: Although many large-scale genome-wide association studies (GWASs) have been performed, only a few studies have successfully identified replicable, large-impact hypertension loci; even fewer studies have been done on Chinese subjects. Young-onset hypertension (YOH) is considered to be a more promising target disorder to investigate than late-onset hypertension because of its stronger genetic component.

Methods: To map YOH genetic variants, we performed a 3-stage study combining 1st-stage multilocus GWASs, 2nd-stage gene expression analysis, and 3rd-stage multilocus confirmatory study.

A comprehensive framework for prioritizing variants in exome sequencing studies of Mendelian diseases.

Exome sequencing strategy is promising for finding novel mutations of human monogenic disorders. However, pinpointing the casual mutation in a small number of samples is still a big challenge. Here, we propose a three-level filtration and prioritization framework to identify the casual mutation(s) in exome sequencing studies.

GATES: a rapid and powerful gene-based association test using extended Simes procedure.

The gene has been proposed as an attractive unit of analysis for association studies, but a simple yet valid, powerful, and sufficiently fast method of evaluating the statistical significance of all genes in large, genome-wide datasets has been lacking. Here we propose the use of an extended Simes test that integrates functional information and association evidence to combine the p values of the single nucleotide polymorphisms within a gene to obtain an overall p value for the association of the entire gene. Our computer simulations demonstrate that this test is more powerful than the SNP-based test, offers effective control of the type 1 error rate regardless of gene size and linkage-disequilibrium pattern among markers, and does not need permutation or simulation to evaluate empirical significance.

HGD-Chn: The Database of Genome Diversity and Variation for Chinese Populations.

The Database of Genome Diversity and Variation for Chinese Populations is toward a more efficient utilization and sharing of the valuable yet diminishing genetic resources in China (including sample information of healthy populations, healthy pedigrees, disease population and disease pedigrees; genomic diversity data; disease-related allelic and haplotype data). Organization of the database can be divided into two parts: (1) Genetic resources of healthy people--Organizing genetic resources of healthy people. A variety of genetic markers (VNTR, STR, SNP, HLA, and enzyme markers, etc.

[Genetic polymorphisms of ten X chromosome STR loci in Hunan Tujia population and their forensic evaluation].

Genomic DNA was extracted from whole blood of 198 unrelated health individuals of Tujia ethnic group from south China's Hunan Province. Genotyping and detection of PCR products were carried out on denaturing polycrylamide gel electrophoresis followed by silver staining. Allele frequencies and genotype frequencies were computed.

[Validation the haplotype polymorphisms of the DXS7424-DXS101 on X-chromosome].

Objective: To validate the genetic characteristics and distribution of DXS7424-DXS101 on X chromosome in Han population.

Methods: DXS7424 and DXS101 loci were genotyped by PCR, PAGE and silvers stain methods. Their genetic parameters were analyzed by Arlequin software.

[Genetic polymorphisms of 9 X-chromosome short tandem repeat loci in a Inner Mongolia Ewenki population and their forensic evaluation].

Objective: To investigate the alleles and genotypes frequency of 9 short tandem repeat (STR) loci on the X chromosome (DXS6789, DXS101, DXS8378, DXS7132, DXS7133, DXS7423, DXS6804, DXS6799, HPRTB) of Ewenki individuals living in Inner Mongolia Autonomous Region of China.

Methods: The 9 X-chromosomal STR loci were analyzed with polymerase chain reation (PCR), followed by polyacylamide gel electrophoresis and silver staining. Software SPSS13.

[The application of statistical approaches in studying population genetics with STR data].

As high polymorphism markers, STR loci have been widely used in studying population genetics. This review summarizes various genetic diversity parameters and analysis methods regarding to genotype frequency and allele frequency, including heterozygosity, polymorphism information content (PIC), linkage disequilibrium coefficients, inbreeding coefficients, genetic distance and fixation indices. The methods of statistical analysis included principal component analysis, phylogenetic trees, analysis of molecular variance (AMOVA), R matrix, GIS and spatial autocorrelation.

[Study on SNP polymorphism of mitochondrial DNA D-loop region from Nu ethnic population in Yunnan of China].

Objective: To investigate the mitochondrial single nucleotide polymorphism (SNP)of Chinese Nu ethnic population from Yunnan region of China and to provide basic database for ethnic origin investigation and forensic purpose.

Methods: Genomic DNA from the whole blood of 87 unrelated individuals was extracted by standard chelex-100. The sequence polymorphism was analyzed by PCR-based assay and using ABI 3730 Analyzer to detect many number of relatively common point mutations.