No association between schizophrenia and homozygosity at the D3 dopamine receptor gene

The D₃ dopamine receptor gene is an important candidate gene for schizophrenia, since (because of its almost exclusive expression in the limbic system) it combines the dopamine receptor hypothesis with the limbic system hypothesis of schizophrenia. A BalI restriction fragment length polymorphism of the D₃ dopamine receptor gene has been typed in 107 schizophrenic patients and 98 normal controls from Sichuan (China). With regard to alleles or genotypes, no significant differences were obtained between controls from Europe and China, between patients and controls, and between patient subgroups and controls. These results indicate a lack of association between schizophrenia and the D₃ dopamine receptor gene in our sample. Our findings are at variance with reports of a significant excess of homozygosity at the D₃ dopamine receptor gene in schizophrenic patients from Wales (United Kingdom) and Alsace (France). In conclusion, further studies will be needed with larger samples of patients from Wales and Alsace as well as with samples of different racial groups to prove or disprove the initial positive association between schizophrenia and genotypes of the D₃ dopamine receptor gene. © 1993 Wiley-Liss, Inc.     

Genetic control of serum IgE levels: a study of low molecular weight protein tyrosine phosphatase

Protein tyrosine phosphatases (PTPases) have recently been recognized as important modulators of various signal transduction pathways in immune cells. Genetic polymorphisms have been described in genes codifying for members of this family of enzymes, and the genetics of PTPases is predicted to play an important role in the etiology of immune diseases and of their clinical variability. The low molecular weight protein tyrosine phosphatase (ACP1 or LMPTP) is one of the few PTPases with a known genetic polymorphism, and has been proposed to be associated with atopic dermatitis in a small sample from an Italian population. In this paper we describe the association of the ACP1 polymorphism with total IgE levels in two independent samples from English and Italian populations. In both the samples the mean value of serum IgE is lower among subjects carrying the BC genotype than in other ACP1 genotypes. The BC genotype is associated with the highest total ACP1 enzymatic activity. Our data suggest that one or both of the ACP1 isoforms exert an inhibitory role on some signal transduction pathway relevant for IgE hyperproduction.     

Juvenile sudden death in a family with polymorphic ventricular arrhythmias caused by a novel RyR2 gene mutation: evidence of specific morphological substrates

We report on a family with a history of sudden death and effort-induced polymorphic ventricular arrhythmias. The index case was a 17-year-old boy who died suddenly and at postmortem had evidence of fibrofatty replacement in the right ventricular free wall, consistent with arrhythmogenic right ventricular cardiomyopathy, as well as calcium phosphate deposits within the myocytes. A molecular genetics investigation carried out in the paraffin-embedded myocardium of the subject and in blood samples of family members disclosed a missense mutation in exon 3 (230C-->T; A77V) of the cardiac ryanodine receptor type 2 gene. The carriers showed effort-induced polymorphic ventricular tachycardia in the setting of normal resting electrocardiogram and trivial echocardiographic abnormalities, consistent with catecholaminergic polymorphic ventricular tachycardia. The observation of both arrhythmogenic right ventricular cardiomyopathy type 2 and catecholaminergic polymorphic ventricular tachycardia in the same family suggests that the two entities might correspond to different degrees of phenotypic expression of the same disease. This experience underscores the importance of a precise autopsy diagnosis in the case of sudden cardiac death, including molecular genetics, and the mission of pathologists to guide further clinical investigation of family members.     

Genetics of congenital hyperinsulinism

Congenital hyperinsulinism (CHI) is a clinically and genetically heterogeneous entity and causes severe hypoglycemia in neonates and infants. The clinical heterogeneity is manifested by severity ranging from extremely severe, life-threatening disease to very mild clinical symptoms, which may even be difficult to identify. Furthermore, clinical responsiveness to medical and surgical management is extremely variable. Recent discoveries have begun to clarify the molecular etiology of this disease in about 50% of cases. Mutations in five different genes have been identified in patients with this clinical syndrome. Most cases are caused by mutations in the genes ABCC8 and KCNJ11 coding for either of the two subunits of the beta-cell KATP channel (SUR1 and Kir6.2). Recessive mutations of the beta-cell K(ATP) channel genes cause diffuse HI, whereas loss of heterozygosity together with inheritance of a paternal mutation causes focal adenomatous HI. In other cases, CHI is caused by mutations in genes coding for the beta-cell enzymes glucokinase (GK), glutamate dehydrogenase (GDH), and SCHAD. However, for as many as 50% of the cases, no genetic etiology has yet been determined. The study of the genetics of this disease has provided important new information regarding beta-cell physiology.     

Protective efficacy in chickens, geese and ducks of an H5N1-inactivated vaccine developed by reverse genetics

We generated a high-growth H5N1/PR8 virus by plasmid-based reverse genetics. The virulence associated multiple basic amino acids of the HA gene were removed, and the resulting virus is attenuated for chickens and chicken eggs. A formalin-inactivated oil-emulsion vaccine was prepared from this virus. When SPF chickens were inoculated with 0.3 ml of the vaccine, the hemagglutinin-inhibition (HI) antibody became detectable at 1 week post-vaccination (p.v.) and reached a peak of 10log2 at 6 weeks p.v. then slowly declined to 4log2 at 43 weeks p.v. Challenge studies performed at 2, 3 and 43 weeks p.v. indicated that all of the chickens were completely protected from disease signs and death. Ducks and geese were completely protected from highly pathogenic H5N1 virus challenge 3 weeks p.v. The duration of protective immunity in ducks and geese was investigated by detecting the HI antibody of the field vaccinated birds, and the results indicated that 3 doses of the vaccine inoculation in geese could induce a 34 weeks protection, while 2 doses induced more than 52 weeks protection in ducks. We first reported that an oil-emulsion inactivated vaccine derived from a high-growth H5N1 vaccine induced approximately 10 months of protective immunity in chickens and demonstrated that the oil-emulsion inactivated avian influenza vaccine is immunogenic for geese and ducks. These results provide useful information for the application of vaccines to the control of H5N1 avian influenza in poultry, including chickens and domestic waterfowl.     

Detection of sperm in men with Y chromosome microdeletions of the AZFa,AZFb and AZFc regions

BACKGROUND: Y chromosome microdeletions are associated with severe male factor infertility. In this study, the success rate of testicular sperm retrieval was determined for men with deletions of AZF regions a, b or c. METHODS: AZF deletions were detected by PCR of 30 sequence-tagged sites within Yq emphasizing the AZFa, b and c regions. Semen analysis and diagnostic testis biopsy or testicular sperm extraction (TESE) findings were correlated with the specific AZF region deleted. RESULTS: A total of 78 men with AZF deletions included three with AZFa deletion, 11 with AZFb, 42 with AZFc, 16 with AZFb+c and six with Yq (AZFa+b+c). All men with AZFa, AZFb, AZFb+c and Yq deletions were azoospermic and no sperm were found with TESE or biopsy. Of men with isolated AZFc deletion, sperm were found in 75% (9/12) by TESE and 45% (9/20) on biopsy (56% overall); 62% (26/42) were azoospermic and 38% (16/42) severely oligozoospermic. A total of 7 patients with deletion patterns that included the complete AZFa region and 23 that included the complete AZFb region who underwent TESE or biopsy did not have sperm detected by these surgical measures. CONCLUSIONS: Microdeletion of the entire AZFa or AZFb regions of the Y chromosome portends an exceptionally poor prognosis for sperm retrieval, whereas the majority of men with AZFc deletion have sperm within the semen or testes available for use in IVF/ICSI.     

Phylogenetic analysis of mtDNA haplogroup TJ in a Finnish population

An association between mitochondrial DNA (mtDNA) mutations 11778G>A and 14484T>C and mtDNA haplogroup J suggests that this haplogroup harbors substitutions capable of modifying the phenotype of Leber's disease. Our knowledge of the compilation of substitutions in haplogroup J is based on only a small number of complete mtDNA sequences, however. We constructed phylogenetic networks for mtDNA haplogroup TJ that were based on the sequence of the complete coding region and the hypervariable segment I, respectively, in 28 Finnish samples. The networks revealed a subdivision of the haplogroup into subclusters T1, T2, J1, and J2, while comparison of the two networks suggested nine fast evolving nucleotide sites in the hypervariable segment I. Genotypes of patients harboring 11778G>A or 14484T>C were obtained from the literature and were then placed in the network. Only four substitutions were found to be common to the patients, but none of these was unique to haplogroup J. If increased penetrance of the 11778G>A and 14484T>C mutations in patients belonging to haplogroup J is assumed, combinations of ancient substitutions must be implicated. Received: September 29, 2000 / Accepted: November 10, 2000     

Climacteric symptoms in an unselected sample of Swedish women

A questionnaire on climacteric symptoms was sent to every woman living in the city of Linköping, Sweden (120,000 inhabitants) who was born in 1928 or 1930. Of the 1246 women concerned, 1118 (90%) responded. At the time of the survey, 252 women (23%) were pre-menopausal. In the total sample, 10B had undergone hysterectomy and/or bilateral oophorectomy. The median age at natural menopause was 51 yr.

Climacteric symptoms were reported by 75% of the women, the predominating complaints being sweating attacks and hot flushes. Vaginal dryness and tenderness were experienced by 30% of the post-menopausal women, the discomfort tending to become more common as the duration of the post-menopausal period lengthened.

After the menopause, every third woman experienced periods of depression more often than previously. Depression was positively correlated to the severity of the vasomotor symptoms.

Fifty percent of the women expressed interest in receiving oestrogen treatment, although only 7% were using oestrogens at the time of the survey. This discrepancy is probably due to widespread apprehension in Swedish society - shared by the doctors - in regard to ‘hormonal treatment’.     

A whole‐genome linkage scan suggests several genomic regions potentially containing QTLs underlying the variation of stature

The word “serious” appears in laws and policies regarding genetics services but is not defined. Genetics professionals would most likely be consulted if definitions are made. We surveyed all U.S. board‐certified genetics services providers and all members of the European Society of Human Genetics (ESHG), Canadian College of Medical Geneticists (CCMG), and Ibero‐American Society of Human Genetics (IASHG), using anonymous, mailed questionnaires. Respondents were asked to list three conditions they considered lethal, three that were serious but not lethal, and three that were not serious. Of 3,317 asked to respond, 1,481 (45%) returned questionnaires. Analysis was limited to responses of the 1,264 (85%) who saw patients. Respondents listed 537 conditions, with extensive overlap between categories; 46% of conditions listed as serious were also listed as not serious and 41% were listed as lethal. Respondents did not want professional societies, laws, or national ethics committees to define serious. They favored individual patients as decision makers, with the help of individual doctors. Their reasons were that genetic disorders vary in expression, individuals perceive disorders differently, professional or legal definitions could be unfair to minority groups, definitions tend to be inflexible when new treatments appear. In the United States, most would not use a definition of serious to limit reproductive services, carrier screening, or neonatal intensive care; outside the United States, more supported limitations. There is not sufficient consensus among experienced genetics professionals to define serious genetic conditions for purposes of law or policy. Responses point to social and economic influences on perceptions of what constitutes a serious genetic disorder. © 2002 Wiley‐Liss, Inc.     

样本量对等位基因检出数量的影响

以中国37个不同民族9个常染色体STR基因座的群体遗传研究数据资料为例，探讨群体遗传学研究中常染色体STR基因座等位基因检出数量与样本量之间的关系，即样本量对等住基因检出数量的影响。结果显示在一定范围之内，样本量的大小与所观测到的不同基因座等位基因检出数量之间存在正相关关系。当超过一定范围时，样本量的继续增加不再明显影响等位基因的检出数量。杂合度较低的位点随样本量的变化波动较大，杂合度较高的位点随样本量的变化波动较小。