Heterogeneity of genetic associations of CDKAL1 and HHEX with susceptibility of type 2 diabetes mellitus by gender

We examined the genetic associations of previously identified sequence variants with type 2 diabetes mellitus (T2DM) and its potentially genetic heterogeneity by gender in a large-scale cohort. A total of 613 T2DM patients and 8221 control subjects from the Korea Association REsource (KARE) cohort were included in the analysis of genetic association of T2DM with 33 nucleotide polymorphic markers identified by previous studies. The association analysis was further conducted with data partitioned by gender. The association analysis resulted in five nucleotide sequence variants associated with the susceptibility of T2DM after Bonferonni correction (P < 0.0015). One was located near the gene of hematopoietically expressed homeobox (HHEX), and the others were all in the gene of cyclin-dependent kinase 5 regulatory subunit-associated protein 1-like 1 (CDKAL1). Further analysis revealed that the sequence variant (rs5015480) near HHEX and two SNPs (rs7756992 and rs9465871) in CDKAL1 were associated with the susceptibility of T2DM in females (P<0.005), but not in males (P>0.005). We suggested heterogeneous genetic associations of the T2DM susceptibility with the CDKAL1 and HHEX genes by gender.     

基于Internet的遗传疾病登记、随访系统的设计与实现

本系统通过以Internet网为平台,将传统的医院/患者(咨询者)的遗传随访模式转为医院/Internet网/患者(咨询者)的新医疗模式,该系统会大大提高遗传随访的及时性和便利性;同时,会有利于遗传登记的开展,也有利于随访资料的保存。     

Genetic associates/counselors in genetic services

A survey of US directors of genetic services showed that about 38% of the non-physician professionals providing such services are genetic associates/counselors (GAs). Over 90% of GAs appear to be involved in direct human services, rather than in the performance of laboratory procedures or research. Although they wanted GAs to be competent in communication and inter-personal skills, counseling, and community education, employers and potential employers tended to rank a background preparation in and knowledge of psychosocial principles relatively less important than a knowledge of biological principles. The possible consequences of these attitudes are discussed in light of the fact that GAs represent a new profession which is still evolving and struggling to define its professional role in genetic services. Despite some role ambiguities, employers familial with their work expressed a strong vote of confidence in these professionals.     

Knowledge of genetics and attitudes toward genetic testing in two hereditary ataxia (SCA 1) Kindreds

Molecular genetic predictive or prenatal genetic testing is now possible in families with one form of adult-onset, autosomal dominant ataxia (SCA 1). Before the SCA 1 gene was isolated, we began a study of the knowledge of genetics, the perception of the disease, and the intended use of genetic testing among members of two large SCA 1 kindreds. Questionnaires were sent to 210 consenting affected, at-risk, and spouse members of two SCA 1 kindreds; data from the 117 respondents were analyzed on a personal computer. Sixty-nine percent of respondents thought predictive testing (by genetic linkage) should be made available immediately, and 42% thought prenatal testing should be made available. The kindreds differed in several important aspects: knowledge of genetic concepts, family size, and anticipated emotional responses to genetic testing. No respondent had obtained individualized genetic counseling. There is moderate interest in genetic testing for this fatal neurodegenerative disease of adulthood. Members of our kindreds have not received genetic counseling outside of the research setting. Finally, factors specific to a particular kindred may influence or predict individual responses to genetic testing. © 1994 Wiley-Liss, Inc.     

Genetic diseases in Lebanon

Lebanon has a high incidence of common and rare genetic diseases, due probably to the mosaic different ethnic origins and the high rate of consanguineous marriages in certain communities. Two major investigations, exploring the genetic structure of the Lebanese population, indicated the population to be caucasiods (though Oriental traits were found). These investigations involved studies of dermatoglyphics, and type and distribution of genetic markers and protein variants. Recorded genetic diseases, some characteristic of ethnic group or particular to a geographic region include familial paroxysmal polyserositis, familial hypercholesterolemia, hypothroidism, the Dyggve-Melchoir-Clausen syndrome, Sandhoff disease, and various genetic hematologic diseases. Genetic counseling and care to patients with genetic diseases is available in Beirut from the Faculty of Medicine at American University and St. Joseph University. Also, the Lebanese National Council for Scientific Research initiates and finances medical genetics programs.     

Management of copy number variants associated with incomplete penetrance and variable expressivity—Results of a French survey

Increasing interest regarding neurodevelopmental disorders and democratization of chromosomal microarray analysis have led to growing identification of neuro-susceptibility copy number variations (CNVs). These CNVs have incomplete penetrance and variable expressivity (PIEV), which makes phenotypic features hard to predict. The French Consortium “AchroPuce” has provided a list of 17 CNVs that should be considered as PIEV CNVs. This list led to consensual French practices of healthcare professionals in postnatal diagnosis. However, no consensus was established in prenatal diagnosis and fetal pathology. 121 French health professionals were surveyed their opinions and practices regarding reporting of PIEV CNVs to patients, in order to identify key points so as to establish French recommendations. The survey showed that professionals in favor of reporting PIEV CNVs to patients in prenatal diagnosis and fetal pathology (respectively, 76% and 84% of respondents) considered highlighted that multidisciplinary consultation is the main point-of-care management before family survey. This statement is close to recommendations published worldwide. As a consequence, multidisciplinary expertise should be the basis of French recommendations concerning the reporting of PIEV CNVs and genetic counseling in prenatal diagnosis and fetal pathology.     

Distinguishing genetic disease and genetic susceptibility

With the increasing awareness of the involvement of genetic factors in disease, questions arise as to what distinguishes genetic from non-genetic disease, and what constitutes a genetic susceptibility. A general framework, reflecting the structure of biological explanations, is presented in which such distinctions can be made. We conclude that such distinctions are objective and are based on the biological facts; they are not “social constructions” nor do they presuppose resolution of philosophical problems regarding causation. © 1994 Wiley-Liss, Inc.     

GeneTests-GeneClinics: genetic testing information for a growing audience

The development and usage of two companion NIH-funded genetic testing information databases, GeneTests (www.genetests.org) and GeneClinics (www.geneclinics.org), now merged into one web site, reflect the steadily increasing use of genetic testing and the expanding audience for genetic testing information. Established in 1993 as Helix, a genetics laboratory directory of approximately 110 listings, GeneTests has grown into a database of over 900 tests for inherited diseases, a directory of over 500 international laboratories, a directory of over 1,000 U.S. and international genetics clinics, and a resource for educational/teaching materials and reports of summary genetic test data. GeneClinics, founded in 1997 as an expert-authored, peer-reviewed, disease-specific knowledge base relating genetic testing to patient care, has grown steadily, now containing over 130 expert-authored, peer-reviewed full-text entries relating genetic testing information to diagnosis, management, and genetic counseling of specific inherited diseases. In spring 2001 the two databases were merged and in October 2001 the two web sites were merged for the purpose of seamless navigation into the GeneTests-GeneClinics site (www.genetests.org or www.geneclinics.org); the GeneClinics knowledge base was renamed "GeneReviews" to avoid confusion with the U.S. and international clinic directories. As genetic testing has moved steadily out of research venues and into routine medical practice, the user audience for these databases has become international and expansive and includes healthcare providers, patients, educators, policy makers, and the media. The use of these combined resources has grown to approximately 3,200 visits/day.     

Genetic testing for inherited retinal degenerations: Triumphs and tribulations

Inherited retinal degenerations (IRDs) are a genotypically and phenotypically diverse group of conditions. Great strides have been made toward identifying the genetic basis for these conditions over the last 30 years—more than 270 different genes involved in syndromic and nonsyndromic forms of retinal dystrophies have now been identified. The identification of these genes and the improvement of clinical laboratory techniques have led to the identification of the genetic basis of disease in 56–76% of patients with IRDs through next generation sequencing and copy number variant analysis. Genetic testing is an essential part of clinical care for patients affected with IRDs and is required to confirm the diagnosis, understand the inheritance of the condition, and determine eligibility for gene‐specific treatments or clinical trials. Despite the success achieved in determining the genetic cause of these conditions, several challenges remain, which must be considered when providing genetic testing and genetic counseling to patients. For this reason, an integrated team of ophthalmic and genetic clinicians who are familiar with these challenges is necessary to provide optimal comprehensive care to these patients.     

A detailed description of mothers' knowledge before genetic counseling for down syndrome: Part I

This study focuses on counselees' knowledge of the Down syndrome before receiving genetic counseling. Data were collected from 47 mothers of children with the Down syndrome using a structured interview of 13 open-ended questions. This instrument was found to be both internally reliable and consistent. Results of this study document the enormous variation of counselees' knowledge of the Down syndrome before genetic counseling and show that this is positively associated with their educational background. Counselees with more than a high school education knew about 60% of the genetic information pertaining to the diagnosis before genetic counseling, while those with less than a high school education knew only 23% of this information before counseling. These results indicate that the better educated counselees are less apt to need to learn basic genetic information and may seek out genetic counseling services for other reasons. Possible motives are seeking knowledge confirmation, emotional support, and personalization of the information.     

线粒体DNA D-loop区多态性与贵州四个少数民族的遗传关系

目的从母系遗传角度探讨贵州侗族、仡佬族、土家族和彝族群体的遗传结构及遗传分化关系。方法对4个群体108份样本的线粒体DNAD-loop高变区Ⅰ（hypervariable segment Ⅰ，HVSⅠ）进行序列分析，计算核苷酸多态度，并用Neighbor-Joining法构建群体间进化树。结果在所测定的497 bp序列中，共检测出86个变异位点，界定出82种单倍型；根据净遗传距离构建的群体间进化树显示：彝族、土家族和仡佬族紧密地聚在一起，最后与侗族聚类。结论彝族与土家族，可能因为有共同的祖先，或在历史上发生过频繁的基因交流与融合，故亲缘关系非常接近；土家族和仡佬族的亲缘关系较近，可能与地域上的相邻有关；彝族和侗族，可能由于历史起源不同以及存在地理隔离的原因，故亲缘关系最远。     

Degree of genetic homozygosity and distribution of AB0 blood types among patients with spina bifida occulta and spina bifida aperta

Introduction

Assuming that spina bifida (SB) is a genetically controlled disease, the aim of our study was to evaluate the degree of genetic homozygosity and the distribution of AB0 blood types among patients with SB occulta and SB aperta by the homozygously recessive characteristics (HRC) test.

Material and methods

Our study included an analysis of the presence, distribution and individual combination of 15 selected genetically controlled morpho-physiological traits in a sample of 100 patients with SB (SB occulta N = 50 and SB aperta N = 50) and a control group of individuals (N = 100).

Results

We found a statistically significant difference between the mean values for genetic homozygosity (SB 4.5 ±0.3; control 3.0 ±0.2, p < 0.001) and also differences in the presence of certain individual combinations of such traits. In 12 (80.0%) of the 15 observed characteristics, recessive homozygosity was expressed to a greater degree among the group of SB patients, while for 9 (60.0%) of the traits this level of difference was statistically significant (Σ_χ ² = 266.3, p < 0.001). There was no difference in average homozygosity of such genetic markers between groups of SB occulta and SB aperta patients, but the type of individual variation in the two studied groups significantly differed. In the group of patients with SB the frequency of 0 blood group was significantly increased while B blood group was significantly decreased.

Conclusions

Our results clearly show that there is a populational genetic difference in the degree of genetic homozygosity and variability between the group of patients with SB and individuals without clinical manifestations, indicating a possible genetic component in the aetiopathogenesis of spina bifida.     

Psychological and social determinants of women's decisions to undergo genetic counseling and testing for breast cancer

This study examined the demand for breast cancer genetic testing and counseling among Canadian women diagnosed with breast cancer under the age of 50, together with some of the factors predicting both their intentions to be tested and the degree to which they act on their intentions. Participants were 110 women under the age of 50 and comprised of two groups: 1) women diagnosed with breast cancer (BC, n = 60): and 2) an index group of unaffected women from the general population (GP, n = 50). All participants completed a survey that addressed family history of breast and other cancers, demographic variables, knowledge and attitudes about breast cancer, and genetic testing. Members of the BC group were offered genetic counseling and testing for BRCA1 and BRCA2 free of charge. Overall, 60% of participants indicated they would like the test, and 40% either did not want it or were uncertain. Seventy-two percent of women in the BC group wanted to be tested. Of these, only 49% had actually contacted the genetic counselor about testing at follow-up 3-15 months later. Intention to be tested was associated with presence of breast cancer, greater perceived benefits of testing, fewer perceived 'costs' of testing, and higher levels of concern about the risk of relatives developing breast cancer. Actual arranging to meet with the genetic counselor among women in the BC group was associated with fewer perceived costs of having the test. Results suggest a moderate level of interest in gene testing, though intention to be tested may not translate into actual uptake. Women who do choose to have the test may believe the potential 'costs' of using this new genetic technology to be relatively few. This has implications for genetic counselors in terms of providing balanced and complete information to women considering genetic testing for breast cancer susceptibility.     

Impact of genetic counseling: A review of published follow-up studies

Retrospective follow-up studies on the impact of genetic conseling, published since 1970, are reviewed in the present paper. Particular attention has been paid to evaluation of understanding of genetic information, planning of later pregnancies and real changes in family composition. A rather wide divergence was found with regard to these three parameters, probably more related to the design of the studies than to a divergence in counselees' understanding and decisions, emphasizing that more, and especially more methodologically sound studies are necessary to evaluate the impact of genetic counseling.     

Quantitative estimation of the genetic risk associated with the induction of heritable translocations at low-dose exposure: ethylene oxide as an example

This paper explores how quantitative risk assessment methods might be extended to analysis of risks to the human germ line. High inhalation exposures to ethylene oxide are reported to cause heritable translocations in male mice with a steep and nonlinear dose-response-curve. We explore quantitative estimation of risk to humans from low exposures based on these animal data, addressing questions of tissue dosimetry for this alkylating agent, expected equivalency of doses across species, germ-cell sensitivity, and extrapolation of dose-response relationship to low exposure levels. Various dose-response models are discussed in terms of their applicability to genetic end points and their ability to reflect the underlying basis of induced heritable translocations.     

Evaluating empowerment in genetic counseling using patient-reported outcomes

Data about patient reported outcomes from cancer genetics services (CGS) are lacking but are essential to guide service evaluation and improvements. We measured improvement in empowerment, following genetic counseling in Singapore using a culturally-adapted version of the Genetic Counseling Outcome Scale (GCOS-24); and sought to identify factors associated with change in empowerment. The GCOS-24 was administered to 155 patients of the CGS, at pre- and post-counseling or testing timepoints. Of which, 110 patients underwent genetic testing. Individual pre- and post-counseling responses were subjected to Rasch analysis; the scale was subsequently split into cognitive control (CC) and emotional control (EC) domains. Associations of baseline characteristics with changes in pre- and post-CC and EC scores were assessed using multiple regression analysis. Both CC and EC scores showed significant improvement following genetic counseling and testing. While all items in the CC domain of being showed increases at follow-up, aspects of EC related to alleviating negative emotions (P = .88) and hopelessness (P = .2) did not show significant improvement. Our study revealed significant improvement in empowerment in patients who have received cancer genetic counseling, while revealing a need to cultivate hope and facilitate the alleviation of negative emotions in patients during genetic counseling.     

A molecular geneticist's view of complex genomic lesions.

Molecular genetic techniques have been used effectively to study the DNA lesions, many of which are large and complex, that are responsible for human genetic disease. In this workshop we explore some of these techniques, how they are applied to study genetic lesions, and how they may be applied to the needs of genetic toxicology.     

Psychiatric genetic counseling: A mapping exercise

Psychiatric genetic counseling (PGC) is gradually developing globally, with countries in various stages of development. In some, PGC is established as a service or as part of research projects while in others, it is just emerging as a concept. In this article, we describe the current global landscape of this genetic counseling specialty and this field's professional development. Drawing on information provided by expert representatives from 16 countries, we highlight the following: (a) current understanding of PGC; (b) availability of services for patients; (c) availability of training; (d) healthcare system disparities and cultural differences impacting practice; and (e) anticipated challenges going forward.