Studies on the History of Pangda Family in Markham

The famous female writer Ma Lihua in her well- known book The Red Mountain Ranges in East Tibet described the social status and influence of the Pangda family.She wrote:"The famous Pangda family in Tibetan pre-modern society stands on both

Relationship Between Polymorphism of Cystathionine beta Synthase Gene and Congenital Heart Disease in Chinese Nuclear Families

Objective To study the relationship between polymorphism of cystathionine beta synthase （CBS） gene and development of congenital heart disease （CHD）. Methods One hundred and twenty-seven CHD case-parent triads were recruited from Liaoning Province as patient group, and 129 healthy subjects without family history of birth defect were simultaneously recruited as control group together with their biological parents. For all subjects the polymorphism of CBS gene G919A locus was examined by PCR-ARMS method, Results The frequencies of three genotypes （w/w, w/m, and m/m） in control group were 27.2%, 58,4%, and 14.4%, respectively, with no significant difference in gender. A significant difference in the allele frequency was found between CHD patients and controls, the wild allele frequency was 67,9% in patients and 55.7% in controls CHD parents＇ genotype distribution was significantly different from that in controls. Further comparison of each type of CHD showed that genotype frequencies in several CHD subtypes were significantly different from those in their corresponding controls. The results of TDT analysis showed that no allele transmission disequilibrium existed in CHD nuclear families. Conclusions CBS gene G919A mutation is associated with the development of CHD, and the mutated allele may decrease the risk of CHD.

Arrhythmogenic cardiomyopathy with left ventricular involvement versus ischemic heart disease: lessons learned from the family study and the reviewed autopsy of a young male

Ischemic heart disease (IHD) is the leading cause of sudden cardiac death (SCD) and often non-thrombosed severe coronary stenoses with or without myocardial scars are detected.Left dominant arrhythmogenic cardiomyopathy (LDAC) is a life-threating rare disease which has been more thoroughly studied in the last 10years.The macroscopic study of an SCD victim was conducted and re-evaluated 9years later.The cardiological work-up in his firstdegree relatives initially comprised an electrocardiogram (ECG) and an echocardiogram.When they were re-evaluted 9years later,a cardiac magnetic resonance,an ECG-monitoring,an exercise testing and a genetic study were performed and the pedigree was extended accordingly.In 2008,an IHD was suspected in the sports-triggered SCD of a 37-year-old man upon the postmortem (75% stenosis of the left main and circumflex coronary arteries;the subepicardial left ventricular fibrofatty infiltration with mild myocardial degeneration was assumed to be a past myocardial infarction).No cardiomyopathy was identified in any of the two proband's sisters.Nine years thereafter,distant relatives were diagnosed with LDAC due to a pathogenic desmoplakin mutation.The reanalysis of the two sisters showed ventricular arrhythmias in one of them without structural heart involvement and the reviewed postmortem of the proband was reclassified as LDAC based on the fibrofatty infiltration;both were mutation carriers.The completion of the family study on 19 family members yielded one SCD due to LDAC (the proband),three living patients diagnosed with LDAC (two with a defibrillator),one mutation carrier without structural ventricular involvement,and 14 healthy relatives (who were discharged) with a very good co-segregation of the mutation.Although rare,LDAC exists and sometimes its differential diagnosis with iHD has to be faced.Modifying previous postmortem misdiagnoses can help family screening to further prevent SCDs.

Does Population Aging Hinder the Accumulation of Human Capital?Evidence from China

There is no consensus on the impact of population aging on education investment.To explore this question,we first build an overlapping generations(OLG)model to theoretically analyze the effect of population aging on human capital investment in China,and then test our theory by conducting an empirical study based on micro household data.We find the following.(1)Theoretically,the OLG model shows that population aging has a crowding-out effect on education investment.(2)Empirically,the results show that the share of education and training expenditures decreases by 5.27 percentage points as the ratio of old people in the household increases by 100 percentage points,which confirms the crowding-out effect of population aging on human capital investment.(3)The crowding-out effect is far more intense on urban households than on rural households since health care expenditures will be greater in urban areas as population aging increases.(4)A quantile regression indicates that the negative effect of population aging on the share of educational expenditure is concentrated in households with higher shares of education expenditures.We confirm the robustness of our results using regional fixed effect and instrumental variable(Ⅳ)regressions.

Genetic analysis of four consanguineous multiplex families with inflammatory bowel disease

Background:Family studies support a genetic predisposition to inflammatory bowel diseases(IBD),but known genetic variants only partially explain the disease heritability.Families withmultiple affected individuals potentially harbour rare and highimpact causal variants.Long regions of homozygosity due to recent inbreedingmay increase the risk of individuals bearing homozygous loss-of-function variants.This study aimed to identify rare and homozygous genetic variants contributing to IBD.Methods:Four families with known consanguinity and multiple cases of IBD were recruited.In a family-specific analysis,we utilised homozygosity mapping complemented by whole-exome sequencing.Results:We detected a single region of homozygosity shared by Crohn’s disease cases from a family of Druze ancestry,spanning 2.6Mb containing the NOD2 gene.Whole-exome sequencing did not identify any potentially damaging variants within the region,suggesting that non-coding variation may be involved.In addition,affected individuals in the families harboured several rare and potentially damaging homozygous variants in genes with a role in autophagy and innate immunity including LRRK1,WHAMM,DENND3,and C5.Conclusion:This study examined the potential contribution of rare,high-impact homozygous variants in consanguineous families with IBD.While the analysis was not designed to achieve statistical significance,our findings highlight genes or loci that warrant further research.Non-coding variants affecting NOD2 may be of importance in Druze patients with Crohn’s disease.