摘要:

Cytogenetic studies were performed in celiac disease (CD) patients to determine if the presence of chromosome instability is related to the predisposition to cancer. Chromosome aberrations (CA) and sister chromatid exchange (SCE) frequencies in peripheral blood lymphocyte cultures from untreated CD patients and healthy controls were analyzed. Patients showed aberrations in 23% of cells, while only 3% were detected in the control group (p<0.0001). The mean frequencies of gaps, breaks and total CA were found to be higher in CD patients compared to controls (p<0.0001). Breakpoint distribution was nonrandom among chromosomes from celiac patients (p = 0.01), but not among controls (p = 0.04). The frequency of SCE/cell showed a mean value of 6.9 ± 0.6 in CD patients and 7.3 ± 0.2 in controls. No statistical differences were found. Breakpoints involved in CD patients presented a strong coincidence with the location of fragile sites (78.6%) and sites of cancer chromosome rearrangements (57.1%), most of them (75%) associated with malignant non‐Hodgkin lymphomas. These results suggest that CD is a condition with increased chromosome instability characterized by a high level of CA and normal SCE frequencies, probably related to the increased incidence of can

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb03994.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A high quality of cytogenetic preparations is important for maintaining a high standard in the cytogenetic laboratory. In the past, quality has been assessed by visual counting or estimation of the number of bands on chromosomes. In this paper we have counted bands automatically during karyotyping by using the Magiscan chromosome analysis system. A high correlation between automatic and visual counting was found, the automatic counting was reproducible and count figures were comparable when the karyotyping machines were operated by different technicians. The automatic counting procedure has now been included in our routine for 1 year. The highest numbers of bands were counted on slides from peripheral blood, with fewer bands for amniotic fluid and the lowest number for cells from chorionic villi. All three cell types showed significant variations in band number over time, which may be due to changes in weather conditions and/or the reagents used for cell culture, harvest and staining. It is concluded that the automatic counting procedure may be used to monitor the quality of metaphases over time and to set limits for band number on routine preparations acceptale for analysis.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb03995.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Two semen samples from a 47, XXY male were examined using chromosome‐specific DNA probes and fluorescentin situhybridization (FISH) to determine the distribution of sex chromosomes and an autosome (chromosome 17) in the sperm. A motile population of sperm was also prepared from one sample using the swim‐up technique to compare the motile and total sperm populations. Chromosomes were localized using single FISH and a biotinylated chromosome 17 probe (TR17), or double FISH using a biotinylated X chromosome probe (TRX) and a digoxigenin‐labelled Y chromosome probe (HRY). Labelling efficiencies were 95–98%. Ploidy levels were estimated by measurement against a microscope eyepiece graticule. The overall ratio of X‐to Y‐bearing sperm was 47% to 48.4% in the neat samples, and 48.4% to 45.3% in the swim‐up fraction. Neither of the ratios was significantly different from 1:1. The frequencies of monosomic and disomic (but otherwise haploid sperm) were not different from the frequencies we observed in normal donors. In contrast, the frequencies of both diploid and tetraploid cells were increased in the neat samples of the XYY male. In the swim‐up fractions, however, none of these parameters differed from those of ten normal semen donors. These results support the hypothesis that the extra Y chromosome in XYY men is eliminated during

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb03996.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Plasma fibrinogen was determined in 189 twins participating at the Indiana center during the third examination of the NHLBI twin study with a mean age of 63 years. Moderate heritability estimates were obtained from 44 complete MZ pairs and 39 complete DZ pairs. After adjustment of fibrinogen levels for age and other confounding variables related to cardiovascular disease risk, the maximum likelihood heritability estimate was only 30% (p = 0.03). Plasma fibrinogen was most strongly associated with smoking and the presence of diabetes. Omitting all subjects with diabetes or cardiovascular disease further reduced the heritability estimates slightly, and most path models including genetic parameters provided no significant improvement in fit over a model determined solely by random environmental effects. Our results are consistent with the environment rather than genetic influences having a greater influence on the level of plasma fibrinogen.

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb03997.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

The association of polymorphic alleles of the apolipoprotein B gene (Insertion/Deletion‐, Xbal‐, MspI‐, EcoRI‐, and 3′‐VNTR polymorphisms) with variation in lipid concentrations (total cholesterol (T‐C), HDL cholesterol (HDL‐C), and log‐triglycerides (TG)) in plasma was studied in 259 men and 59 women with moderate hypercholesterolemia (T‐C 5.5–8.0 mmol/l and TG<2.5 mmol/l) and ischemic heart disease, especially in relation to the effect of sex and age. The XbaI and the Ins/Del polymorphic alleles were associated with variation in T‐C, but only in patients below the 75th percentile for age. The XbaI and Ins/Del polymorphic alleles were synergistically associated with variation in T‐C: the X+ and the Del alleles were associated with higher cholesterol concentrations. Younger male patients had the highest frequency of haplo‐types including both the X+ and the Del alleles, but the most striking difference was a significantly higher frequency of haplotypes including both the X — and the Ins alleles in female and in older male patients. The heterogeneity of association of polymorphic alleles in the apolipoprotein B gene to complex traits like hypercholesterolemia and ischemic heart disease in this study could explain why in most studies the X+ allele has been associated with higher cholesterol levels, whereas the X — allele has been associated with symptomatic atherosclerosis. The results of our study emphasize the importance of age and sex in measur

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb03998.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

DNA analysis of the low density lipoprotein receptor (LDLR) gene was performed in two persons with familial hypercholesterolemia (FH). Southern blot experiments indicated the heterozygous loss of an EcoRI site in exon 5 of the LDLR gene. Upon amplification and sequencing of exon 5 in both probands, an 87‐bp deletion in a heterozygous state could be evaluated. This is a novel mutation, most probably leading to the formation of a nonfunctional LDLR. Analysis of the deletion breakpoints revealed the presence of a six‐base‐pair consensus sequence 5′TGA/GA/GG/TA/C3′, which is characteristic of small deletions in different geneti

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb03999.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A gene (DYT1) for susceptibility to early‐onset torsion dystonia in Ashkenazi Jewish and Gentile kindreds is situated on chromosome 9q32‐q34 in a 6–7 cM span between markers AK1 and ASS. To determine whether transmission of familial dystonia with myoclonic jerks responsive to alcohol was consistent with a gene in this region, we studied the 37 members of a Swedish family, of whom 20 were so affected. A lod score of<−2.00 from a two‐point linkage analysis with six DNA markers covering a 30 cM span from D9S26 to D9S10 that included the region of the DYT gene indicated that this gene is not located in this region, and that two or more autosomal loci are responsible for hereditary dystonia

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04000.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

A liveborn female with a phenotype suggestive of Down syndrome is reported. Cytogenetic lymphocyte analysis showed a 46,X der(X) karyo‐type. Fluorescencein situhybridization (FISH) with a biotinylated probe specific for chromosome 21 showed no signal on the der(X). This marker was homogeneously painted using a specific probe for X chromosome. In addition, FISH analysis detected telomeres on the rearranged X. Therefore, the proband's karyotype was revaluated as 46,X,del(X) (pter p22.2::p11.3 qter). Cytogenetic analysis of 150 lymphocytes in the mother disclosed a homogeneous 45,X karyotype. FISH analysis of interphase nuclei using the X chromosome painting probe showed two domains of different sizes in 0.8% of cells. This led us to study further metaphases in the mother. In one out of 450 metaphases scored, after FISH with the X chromosome painting probe, the del(X) was observed, confirming that the rearranged X chromosome found in the newborn had segregated from a 45,X/46,X,del(X) mothe

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04001.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

We report on a family with two severe neuromuscular diseases: Duchenne muscular dystrophy (DMD) and acute infantile spinal muscular atrophy (SMA I). One boy has DMD, and his brother died of SMA I at 11 months of age. Both boys had received the same DMD allele from their mother. Analysis of dystrophin by immunohistochemistry and Western blot showed complete lack of dystrophin in both brothers. The mother had a partial deficiency of dystrophin. The boy with SMA I had increased levels of creatine kinase in serum, compatible with DMD, but the muscle biopsy and post‐mortem examination of the spinal cord showed the typical changes of SMA I. There were no cytogenetic abnormalities explaining the occurrence of both DMD and SMA I in this family. Molecular genetic prenatal diagnosis of DMD and SMA I, using analysis of RFLPs and dinucleotide repeats, has been performed in one foetus in the family. The results showed that the foetus had a high risk of developing SMA I. An abortion was planned but the pregnancy was terminated by miscarriag

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04002.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY

摘要:

Von Hippel‐Lindau disease is generally considered to be a condition with very high penetrance, and individuals who live beyond the age of 60 years without showing any features of the disease, despite undoubtedly carrying the gene defect, have not previously been clearly described. The case is presented of a 65‐year‐old woman, who had four siblings affected with von Hippel‐Lindau disease and had six children, three of whom died young with complications of von Hippel‐Lindau disease. Although she is an obligate gene carrier, she has not developed any significant manifestations of the disease despite careful screening for the neurological, retinal and renal comp

ISSN:0009-9163    

DOI:10.1111/j.1399-0004.1994.tb04003.x

出版商:Blackwell Publishing Ltd    

年代:1994

数据来源: WILEY