Genetic Relationships of Ethnic Minorities in Southwest China Revealed by Microsatellite Markers

Population migrations in Southwest and South China have played an important role in the formation of East Asian populations and led to a high degree of cultural diversity among ethnic minorities living in these areas. To explore the genetic relationships of these ethnic minorities, we systematically surveyed the variation of 10 autosomal STR markers of 1,538 individuals from 30 populations of 25 ethnic minorities, of which the majority were chosen from Southwest China, especially Yunnan Province. With genotyped data of the markers, we constructed phylogenies of these populations with both DA and DC measures and performed a principal component analysis, as well as a clustering analysis by structure. Results showed that we successfully recovered the genetic structure of analyzed populations formed by historical migrations. Aggregation patterns of these populations accord well with their linguistic affiliations, suggesting that deciphering of genetic relationships does in fact offer clues for study of ethnic differentiation

Genome-Wide Linkage Scan of a Pedigree with Familial Hypercholesterolemia Suggests Susceptibility Loci on Chromosomes 3q25-26 and 21q22

BACKGROUND: Familial hypercholesterolemia (FH) is a heritable disorder that can increase the risk of premature coronary heart disease. Studies suggest there are substantial genetic heterogeneities for different populations. Here we tried to identify novel susceptibility loci for FH in a Chinese pedigree. METHODOLOGY/PRINCIPAL FINDINGS: We performed a SNP-based genome-wide linkage scan with the Chinese FH pedigree. Two suggestive linkage loci not previously reported were identified on chromosomes 3q25.1-26.1 (NPL = 9.01, nominal P<0.00001, and simulated occurrence per genome scan = 1.08) and 21q22.3 (NPL = 8.95, nominal P<0.00001, and simulated occurrence per genome scan = 1.26). In the interaction analysis with a trimmed version of the pedigree, we obtained a significantly increased joint LOD score (2.70) compared with that obtained when assuming the two loci uncorrelated, suggesting that more than one locus was involved in this pedigree. Exon screening of two candidate genes ABCG1 and LSS from one of the suggestive region 21q22 didn't report any causative mutations. CONCLUSIONS/SIGNIFICANCES: These results confirm complex etiologies and suggest new genetic casual factors for the FH disorder. Further study of the two candidate regions is advocated

On the Origin of Tibetans and Their Genetic Basis in Adapting High-Altitude Environments

Since their arrival in the Tibetan Plateau during the Neolithic Age, Tibetans have been well-adapted to extreme environmental conditions and possess genetic variation that reflect their living environment and migratory history. To investigate the origin of Tibetans and the genetic basis of adaptation in a rigorous environment, we genotyped 30 Tibetan individuals with more than one million SNP markers. Our findings suggested that Tibetans, together with the Yi people, were descendants of Tibeto-Burmans who diverged from ancient settlers of East Asia. The valleys of the Hengduan Mountain range may be a major migration route. We also identified a set of positively-selected genes that belong to functional classes of the embryonic, female gonad, and blood vessel developments, as well as response to hypoxia. Most of these genes were highly correlated with population-specific and beneficial phenotypes, such as high infant survival rate and the absence of chronic mountain sickness

Cells Transformed by a v-Myb-Estrogen Receptor Fusion Differentiate into Multinucleated Giant Cells

In order to make conditional alleles of the v-myb oncogene, we constructed and tested avian retroviruses which produce a number of different fusion proteins between v-Myb and the human estrogen receptor (ER). We found that the portion of the ER used in making these fusions profoundly affected their transcriptional activation. However, all the fusions tested were only weakly transforming in embryonic yolk sac assays and there was no direct correlation between the level of transcriptional activation and strength of oncogenic transformation. Nevertheless, transformation by a v-Myb-ER fusion was estrogen dependent, and upon withdrawal of the hormone, monocytic-lineage cells differentiated into multinucleated giant cells. Surprisingly, the withdrawal of estrogen caused a dramatic increase in the stability of the fusion protein, although it remained unable to promote cell growth or block differentiation

A Purified Adenovirus 289-Amino-Acid ElA Protein Activates RNA Polymerase III Transcription In Vitro and Alters Transcription Factor TFIIIC

RESEARCH PAPERWe have previously demonstrated that a purified bacterially synthesized ElA 289-amino-acid protein is capable of stimulating transcription from the promoters of genes transcribed by RNA polymerase II in vitro (R. Spangler, M. Bruner, B. Dalie, and M. L. Harter, Science 237:1044-1046, 1987). In this study, we show that this protein is also capable of transactivating in vitro the adenovirus virus-associated (VA1) RNA gene transcribed by RNA polymerase UI. Pertinent to the transcription of this gene is the rate-limiting component, TFIIIC, which appears to be of two distinct forms in uninfected HeLa cells. The addition of an oligonucleotide containing a TFIIIC binding site to HeLa whole-cell extracts inhibits VAT transcription by sequestering TFIIIC. However, the addition of purified ETA to extracts previously challenged with the TFIIIC oligonucleotide restores the level of VAT transcription. When included in the same reaction, an ElA-specific monoclonal antibody reverses the restoration. Incubation of purified ETA with either HeLa cell nuclear or whole-cell extracts alters the DNA-binding properties of TFIIIC as detected by gel shift assays. This alteration does not occur if ElA-specific antibody and ETA protein are added simultaneously to the extract. In contrast, the addition of this antibody to extracts at a later time does not reverse the alteration observed in the TFIIIC binding activities. Never at any time did we note the formation of novel TFIIIC-promoter complexes after the addition of ETA to nuclear extracts. These results clearly establish that ETA mediates its effect on VAT transcription through TFIIIC in a very rapid yet indirect manner. The results also establish that a bacterially produced ETA protein can directly participate in RNA polymerase II transcription without the requirement of celiular protein synthesis or other viral proteins.RUTGERS UNIVERSITY SCHOOL OF MEDICINE (UMDNJ) and THE CLEVELAND CLINIC FOUNDATION (CCF

A preliminary study of copy number variation in Tibetans.

Genetic features of Tibetans have been broadly investigated, but the properties of copy number variation (CNV) have not been well examined. To get a preliminary view of CNV in Tibetans, we scanned 29 Tibetan genomes with the Illumina Human-1 M high-resolution genotyping microarray and identified 139 putative copy number variable regions (CNVRs), consisting of 70 deletions, 61 duplications, and 8 multi-allelic loci. Thirty-four of the 139 CNVRs showed differential allele frequencies versus other East-Asian populations, with P values <0.0001. These results indicated a distinct pattern of CNVR allele frequency distribution in Tibetans. The Tibetan CNVRs are enriched for genes in the disease class of human reproduction (such as genes from the DAZ, BPY2, CDY, and HLA-DQ and -DR gene clusters) and biological process categories of "response to DNA damage stimulus" and "DNA repair" (such as RAD51, RAD52, and MRE11A). These genes are related to the adaptive traits of high infant birth weight and darker skin tone of Tibetans, and may be attributed to recent local adaptation. Our results provide a different view of genetic diversity in Tibetans and new insights into their high-altitude adaptation

GO term enrichment of genes within Tibetan CNVRs.

<p>GO term enrichment of genes within Tibetan CNVRs.</p