Community genetics最新文献

Objective: To assess the attitudes of Saudi parents towards prenatal diagnosis and termination of pregnancy for a range of different genetic disorders.

Methods: Two hundred Saudi parents (100 fathers and 100 mothers) completed a structured questionnaire which sought their views about each of 30 different conditions.

Results: The great majority of people would consider a termination of pregnancy for at least one of the conditions studied. Mothers and fathers held similar attitudes towards prenatal diagnosis, but mothers' attitudes towards termination of pregnancy were more favourable. Parents' collective attitudes towards prenatal diagnosis and towards termination of pregnancy were correlated.

Conclusions: Saudi parents are favourably inclined towards prenatal diagnosis, and consider termination of pregnancy to be acceptable for some conditions. New technologies provide parents with more reproductive choices but also present them with more dilemmas.

Background: Accurate family history information is required for adequate breast and colorectal cancer risk assessments. Few studies have examined the comprehensiveness of the family medical history interview in primary care.

Methods: We compared family cancer history information collected through a self-completed survey with that documented within medical charts for 310 patients.

Results: Forty-three percent (18/42) of individuals at increased risk for breast or colorectal cancer based on their family history had documentation of this risk within their chart. Age of cancer diagnosis was recorded for 40% (50/124) of affected relatives identified by chart review compared with 81% (203/252) identified through the survey (p < 0.0001).

Conclusions: Over half of the individuals at increased risk for breast or colorectal cancer based on their family history did not have documentation of this risk within their medical record, and the age of relatives at diagnosis was frequently missing.

Between 2001 and 2005, 6,166 females underwent cystic fibrosis (CF) carrier screening at our institution. Only 36% were Caucasian. We identified 143 carrier females and subsequently tested 85 of their partners. The observed carrier frequency was not significantly different than expected for any racial or ethnic group tested. We identified 6 positive couples (5 Caucasian, 1 Arab American) and 1 affected fetus. In just under 4 years, our institution spent approximately $334,000 on CF population screening. Comparing this to the lifetime medical cost for a CF patient, CF population-based carrier screening is cost effective at our institution, despite the high number of non-Caucasians being screened.

Objectives: This study was conducted to determine the frequency of CYP2C9 alleles in Omani patients receiving warfarin and to correlate genotyping data with warfarin dosage. The Omani population has Asian and African ethnicities.

Methods: CYP2C9 genotypes were determined by the polymerase chain reaction restriction fragment length polymorphism method. Non-parametric Kruskal-Wallis test was used to compare groups of continuous data for significance differences.

Results: Genotyping data showed that 12.7 and 5.8% of the samples were heterozygous for the CYP2C9*2 and CYP2C9*3 alleles, respectively. The CYP2C9*2 allele frequency was 0.074 in our population. It was 0.029 for CYP2C9*3.

Conclusion: This is the first report on the presence of CYP2C9*2 allele homozygocity in any Asian or African population.

Objectives: It was the aim of this study to assess the attitudes of doctors, medical students, lawyers, parliament members and parents of thalassemic children towards genetic diagnosis in Pakistan.

Study design: A cross-sectional descriptive survey was conducted among representative samples.

Results: Five hundred and seventy doctors, 49 lawyers, 178 medical students, 89 parents of thalassemic children and 16 members of parliament (MPs) were included in the survey. The groups showed considerable difference in their attitudes towards different aspects of the issue. A large proportion (88.5%) agreed to the idea of genetic diagnostic screening, especially the parents of thalassemic patients. Premarital carrier screening was favored by 77% of the respondents. Prenatal screening was most favored by the parents of thalassemic children (94.4%). Likewise, a majority of parents of thalassemic children were in favor of abortion in case of an affected fetus. Genetic self-screening was also favored most by the parents of thalassemic patients (78.2%). Only 24% of the doctors favored making genetic screening mandatory, whereas 63% of the parents agreed to the idea.

Conclusion: Attitudes regarding genetic diagnosis are markedly different among various societal groups in Pakistan. The parents of the affected children strongly favor genetic screening as does the medical community, though not as strongly as the parents. The legislative groups, particularly the MPs, are reserved in their support. Genetic diagnosis can help decrease the disease burden in the future. However, it raises a number of ethical issues, which need to be addressed. It is important to educate the population about potential benefits as well as ethical dilemmas involved so that the general public is able to make the right decisions for themselves and their families.

The population in Jordan mounted from half a million in 1952 to 5.3 millions in 2004 and is composed of a variety of ethnic groups, the majority being Arabs. Couples nowadays tend to have fewer children, with the total fertility rate falling from 7.4 in 1976 to 3.7 in 2004. Consanguineous marriages are traditionally favored, with the preferred marriage partner being the offspring of the father's brother. First-cousin marriages declined from 28.5% for marriages contracted between 1950 and 1979 to 19.5% for marriages contracted after 1980. In the overall population, carrier rates for beta-thalassemia, alpha-thalassemia and sickle cell anemia are in the range of 2-4%, 3.2-12% of males have glucose-6-phosphate dehydrogenase deficiency, and the prevalences for familial Mediterranean fever and cystic fibrosis were estimated at around 0.04% each. A mandatory premarital screening program for beta-thalassemia carriers commenced in June 2004. The high consanguinity rate and the large family size in Jordan have contributed to the description of a number of rare and new autosomal recessive conditions. Genetic services in Jordan are still scarce and do not cover all the country due to the major impediments of a paucity of resources and trained health professionals in the area of medical genetics. The demographic data suggest that the health system in Jordan is capable of introducing some basic community genetic services into the primary health care program through comprehensive and cost-effective programs.

The completion of the human genome project has spurred new thinking about launching large-scale cohort studies; as proposed, these studies will differ from past large-scale cohort studies and will focus primarily on how genetic variation interacts with environmental exposures to affect the risk for common human diseases. There is no single 'best design' for large-scale studies of gene-environment interactions. Some studies are best performed in cohort studies where unbiased information can be collected on individuals years before disease onset. Other studies may be most efficiently done with a case-control design using currently available automated data. Population-based biobanks with nested case-control or case-cohort studies offer distinct advantages to some of the resource-intensive large-scale cohort studies under consideration, and may be more acceptable to many of the countries around the world currently considering such projects.

Background: Familial aggregation of congenital heart disease (CHD) has been well described in different populations, in particular those with a high consanguinity rate. Extensive genetic study of affected families has improved the understanding of basic genetics of different cardiac lesions.

Objective: To identify the role of consanguinity as a risk factor among familial cases of CHD in a stable outpatient population of a tertiary care center in the Eastern Province of Saudi Arabia.

Methods: All familial cases of CHD seen over 5 years (1996-2000) in the Division of Pediatric Cardiology were identified. The presence or absence of parental consanguinity (first cousin marriage) was defined in each of these families.

Results: Ninety-three cases were identified in 37 families. Twenty-three (62%) families resulted from consanguineous marriages. In 4 families where there were 2 marriages, the affected children came from the consanguineous marriage in 3 of these families. Discordant lesions occur only among non-consanguineous cases, while all consanguineous cases were concordant. Five sets of twins of the same sex (one set are monozygotic by DNA analysis) occurred among consanguineous marriages, in 3 of these both twins were affected with the same disease. Affected parents were seen in 2 families with consanguineous marriage and none in the non-consanguineous marriages. The prevalence of dilated cardiomyopathy was much higher among consanguineous cases (26 vs. 2).

Conclusions: Familial aggregation of congenital heart disease is common in our population. Consanguinity is common in these families, and the distribution of congenital heart disease differs in this subgroup compared to the rest of the familial cases. Further genetic studies of these families may help to shed more light on basic genetics and the specific pathogenetic mechanisms involved.

Vaccines are the most powerful means to prevent and diminish the burden of infectious disease. However, there are limitations to their use: vaccines are not yet available for all infectious diseases (including human immunodeficiency virus and respiratory syncytial virus), they sometimes lack efficacy, the response to vaccination is limited by maternal antibodies in very young infants, and the response to vaccination is variable or may even be absent in some individuals. This review focuses on genetic factors that determine the variable response to vaccination. The highly polymorphic human leukocyte antigen system, which is involved in antigen presentation, has been researched most in this aspect, and clearly affects the response to vaccination. Other, but less polymorphic pathways involved are the Toll-like receptor pathway, which is involved in antigen recognition and stimulation of the immune system, and the cytokine immunoregulatory network. The heritability, or the proportion of total variance that is due to additive genetic factors, appears to be particularly large for vaccine-induced antibody responses in young infants compared with cell-mediated responses and antibody responses in older, immunologically more mature individuals. Both antibody and cell-mediated responses are not only affected by loci within, but also strongly by loci outside the human leukocyte antigen system. Because most genes that are important in influencing immune responses to vaccination are still unknown, clearly more work is required. A better understanding of the factors that determine an effective response to vaccination may lead to the identification of specific genes and pathways as targets for the development of novel more uniformly effective vaccines.

Objective: To collect data on the practices of molecular genetic testing (MGT) laboratories for the development of national and international policies for quality assurance (QA).

Methods: A web-based survey of MGT laboratory directors (n = 827; response rate 63%) in 18 countries on 3 continents. QA and reporting indices were developed and calculated for each responding laboratory.

Results: Laboratory setting varied among and within countries, as did qualifications of the directors. Respondents in every country indicated that their laboratory receives specimens from outside their national borders (64%, n = 529). Pair-wise comparisons of the QA index revealed a significant association with the director having formal training in molecular genetics (p < 0.005), affiliation with a genetics unit (p = 0.003), accreditation of the laboratory (p < 0.005) and participation in proficiency testing (p < 0.005). Research labs had a lower mean report score compared to all other settings (p < 0.05) as did laboratories accessioning <150 samples per year.

Conclusion: MGT is provided under widely varying conditions and regulatory frameworks. The data provided here may be a useful guide for policy action at both governmental and professional levels.