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G B Van Ommen 《American journal of human genetics》1987,41(4):689-691
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Autosomal trisomy causes a large proportion of all human pregnancy loss and so is a significant source of lethality in the human population. The autosomal trisomy syndromes each have a different phenotype and are probably caused by the effects of specific genes that are present in three copies, rather than the normal two. Identifying these genes will require the application of classical genetic and new genome-manipulation approaches. Recent advances in chromosome engineering are now allowing us to create precisely defined autosomal trisomies in the mouse, and so provide new routes to identifying the critical, dosage-sensitive genes that are responsible for these highly deleterious, yet very common, syndromes. 相似文献
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The karyotypes of 100 males and 100 females, each assembled by the trypsin banding method, are examined in a study designed to investigate sex differences among autosomes. It is shown that female autosomes are consistently longer than those of the males, with respect to both the short and long arm measurements. In addition, discriminant analysis is used to distinguish between the male and female karyotypes. We find that, using autosomal measurements alone, this can be done with a high probability of success. 相似文献
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Summary Association, in one patient, of the following malformations: brachydactylia of all segments but terminal phalanges; proximal symphalangism of many fingers and toes; abnormalities of carpal and tarsal bones; partial duplication of both big toes; mild hypertelorism. Genetic transmission seems to be recessive autosomal. 相似文献
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Early-onset autosomal dominant Alzheimer disease: prevalence, genetic heterogeneity, and mutation spectrum. 总被引:18,自引:0,他引:18
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D Campion C Dumanchin D Hannequin B Dubois S Belliard M Puel C Thomas-Anterion A Michon C Martin F Charbonnier G Raux A Camuzat C Penet V Mesnage M Martinez F Clerget-Darpoux A Brice T Frebourg 《American journal of human genetics》1999,65(3):664-670
To determine the prevalence of early-onset Alzheimer disease (EOAD) and of autosomal dominant forms of EOAD (ADEOAD), we performed a population-based study in the city of Rouen (426,710 residents). EOAD was defined as onset of disease at age <61 years, and ADEOAD was defined as the occurrence of at least three EOAD cases in three generations. Using these stringent criteria, we calculated that the EOAD and ADEOAD prevalences per 100,000 persons at risk were 41.2 and 5.3, respectively. We then performed a mutational analysis of the genes for amyloid precursor protein (APP), presenilin 1 (PSEN1), and presenilin 2 (PSEN2) in 34 families with ADEOAD ascertained in France. In 19 (56%) of these families, we identified 16 distinct PSEN1 missense mutations, including 4 (Thr147Ile, Trp165Cys, Leu173Trp, and Ser390Ile) not reported elsewhere. APP mutations, including a novel mutation located at codon 715, were identified in 5 (15%) of the families. In the 10 remaining ADEOAD families and in 9 additional autosomal dominant Alzheimer disease families that did not fulfill the strict criteria for ADEOAD, no PSEN1, PSEN2, or APP mutation was identified. These results show that (1) PSEN1 and APP mutations account for 71% of ADEOAD families and (2) nonpenetrance at age <61 years is probably infrequent for PSEN1 or APP mutations. 相似文献
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A kinky-coat mutant was discovered at the fifth generation of the BAN strain originating from wild musk shrews (Suncus murinus) in Bangladesh. Mating experiments indicated that the kinky-coat character is controlled by a single autosomal recessive gene designated kc (kinky coat), which is not allelic to the gene ch (curly hair) previously reported in the Tr strain derived from wild musk shrews on Taramajima Island, Japan. Because the kc/kc homozygotes were fully fertile and viable, the kc gene should be useful as a genetic marker in linkage studies. In external appearance, homozygotes were characterized by curly vibrissae, somewhat unkept coat hair, and wavy long hair on the tail. Both the length and width of coat hair did not differ significantly between homozygous and normal shrews. Light microscopic observations showed that shafts of the kc coat hair are wavy and often have small swellings with disorganization of the medullary structure. Scanning electron microscopic examinations further revealed that the shafts of the vibrissae, coat hair, and tail hair have abnormalities such as longitudinal fissures, twists, and hollows. It is clear that these modifications caused waviness or curling of the shafts of the three kinds of hairs observed. 相似文献
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Novel locus for autosomal dominant hereditary spastic paraplegia, on chromosome 8q. 总被引:11,自引:2,他引:9
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P Hedera S Rainier D Alvarado X Zhao J Williamson B Otterud M Leppert J K Fink 《American journal of human genetics》1999,64(2):563-569
Hereditary spastic paraplegia (HSP) is a clinically and genetically heterogeneous group of disorders characterized by insidiously progressive spastic weakness in the legs. Genetic loci for autosomal dominant HSP exist on chromosomes 2p, 14q, and 15q. These loci are excluded in 45% of autosomal dominant HSP kindreds, indicating the presence of additional loci for autosomal dominant HSP. We analyzed a Caucasian kindred with autosomal dominant HSP and identified tight linkage between the disorder and microsatellite markers on chromosome 8q (maximum two-point LOD score 5.51 at recombination fraction 0). Our results clearly establish the existence of a locus for autosomal dominant HSP on chromosome 8q23-24. Currently this locus spans 6.2 cM between D8S1804 and D8S1774 and includes several potential candidate genes. Identifying this novel HSP locus on chromosome 8q23-24 will facilitate discovery of this HSP gene, improve genetic counseling for families with linkage to this locus, and extend our ability to correlate clinical features with different HSP loci. 相似文献
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A genome-wide search for genes predisposing to manic-depression, assuming autosomal dominant inheritance. 总被引:3,自引:2,他引:1
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H Coon S Jensen M Hoff J Holik R Plaetke F Reimherr P Wender M Leppert W Byerley 《American journal of human genetics》1993,52(6):1234-1249
Manic-depressive illness (MDI), also known as "bipolar affective disorder," is a common and devastating neuropsychiatric illness. Although pivotal biochemical alterations underlying the disease are unknown, results of family, twin, and adoption studies consistently implicate genetic transmission in the pathogenesis of MDI. In order to carry out linkage analysis, we ascertained eight moderately sized pedigrees containing multiple cases of the disease. For a four-allele marker mapping 5 cM from the disease gene, the pedigree sample has > 97% power to detect a dominant allele under genetic homogeneity and has > 73% power under 20% heterogeneity. To date, the eight pedigrees have been genotyped with 328 polymorphic DNA loci throughout the genome. When autosomal dominant inheritance was assumed, 273 DNA markers gave lod scores < -2.0 at recombination fraction (theta) = .0, 174 DNA loci produced lod scores < -2.0 at theta = .05, and 4 DNA marker loci yielded lod scores > 1 (chromosome 5--D5S39, D5S43, and D5S62; chromosome 11--D11S85). Of the markers giving lod scores > 1, only D5S62 continued to show evidence for linkage when the affected-pedigree-member method was used. The D5S62 locus maps to distal 5q, a region containing neurotransmitter-receptor genes for dopamine, norepinephrine, glutamate, and gamma-aminobutyric acid. Although additional work in this region may be warranted, our linkage results should be interpreted as preliminary data, as 68 unaffected individuals are not past the age of risk. 相似文献
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M C Siomi H Siomi W H Sauer S Srinivasan R L Nussbaum G Dreyfuss 《The EMBO journal》1995,14(11):2401-2408
Fragile X mental retardation syndrome, the most common cause of hereditary mental retardation, is directly associated with the FMR1 gene at Xq27.3. FMR1 encodes an RNA binding protein and the syndrome results from lack of expression of FMR1 or expression of a mutant protein that is impaired in RNA binding. We found a novel gene, FXR1, that is highly homologous to FMR1 and located on chromosome 12 at 12q13. FXR1 encodes a protein which, like FMR1, contains two KH domains and is highly conserved in vertebrates. The 3' untranslated regions (3'UTRs) of the human and Xenopus laevis FXR1 mRNAs are strikingly conserved (approximately 90% identity), suggesting conservation of an important function. The KH domains of FXR1 and FMR1 are almost identical, and the two proteins have similar RNA binding properties in vitro. However, FXR1 and FMR1 have very different carboxy-termini. FXR1 and FMR1 are expressed in many tissues, and both proteins, which are cytoplasmic, can be expressed in the same cells. Interestingly, cells from a fragile X patient that do not have any detectable FMR1 express normal levels of FXR1. These findings demonstrate that FMR1 and FXR1 are members of a gene family and suggest a biological role for FXR1 that is related to that of FMR1. 相似文献
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M Mathieu A Goldfarb P Berquin B Boudailliez B Labeille C Piussan 《Genetic counseling (Geneva, Switzerland)》1991,2(2):115-118
Two brothers are described with trichomegaly, early pigmentary degeneration of the retina, growth retardation, anterior pituitary deficiencies and peripheral neuropathy. This syndrome, initially reported in a boy by Olivers and Mac Farlane in 1965 (6), and thereafter in six sporadic cases of both sexes, is not associated with a recognizable chromosomal defect. The present report of two brothers of healthy parents with negative familial history suggests an autosomal recessive mode of inheritance of this entity. 相似文献
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We study levels of X-linked vs. autosomal diversity using a model developed to analyze the hitchhiking effect. Repeated bouts of hitchhiking are thought to lower X-linked diversity for two reasons: first, because sojourn times of beneficial mutations are shorter on the X, and second, because adaptive substitutions may be more frequent on the X. We investigate whether each of these effects does, in fact, cause reduced X-linked diversity under hitchhiking. We study the strength of the hitchhiking effect on the X vs. autosomes when there is no recombination and under two different recombination schemes. When recombination occurs in both sexes, X-linked vs. autosomal diversity is reduced by hitchhiking under a broad range of conditions, but when there is no recombination in males, as in Drosophila, the required conditions are considerably more restrictive. 相似文献
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R M Couch I A Hughes D J DeSa A Schiffrin H Guyda J S Winter 《American journal of human genetics》1986,39(6):811-816
Eighteen members of an extended pedigree have been found to have a form of euthyroid adolescent multinodular goiter. Histological examination showed multiple adenomata with areas of epithelial hyperplasia, hemorrhage, and calcification. In two subjects there were focal areas of epithelial hyperplasia reminiscent of low-grade papillary carcinoma, but capsular and vascular invasion was not found. The pattern of inheritance appeared to be autosomal dominant, with diminished penetrance in males. Although the patients were euthyroid, the likely basis for this disorder is an abnormality in thyroglobulin structure and function. 相似文献
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In a consecutive series of 592 karyotyped spontaneous abortions, ten of 103 autosomal trisomies were mosaic, with a normal cell line also present. The frequency of mosaicism (10%) is much higher than that reported in Down syndrome, but similar to that reported in amniotic fluid cultures and in induced abortions. The most likely explanations for this discrepancy are (1) previous underestimation of mosaicism in live births or (2) mosaicism which is often restricted to extraembryonic fetal tissue. 相似文献
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D J Schaid S K McDonnell M L Blute S N Thibodeau 《American journal of human genetics》1998,62(6):1425-1438
A family-history cancer survey was conducted on 5,486 men who underwent a radical prostatectomy, for clinically localized prostate cancer, in the Department of Urology at the Mayo Clinic during 1966-95; 4,288 men responded to the survey. Complex segregation analysis was performed to assess the genetic basis of age at diagnosis and the familial clustering of prostate cancer. For the total group, no single-gene model of inheritance clearly explained familial clustering of disease, which could be partly explained by lack of Hardy-Weinberg equilibrium, with an excess of homozygotes. After accounting for deviations from Hardy-Weinberg equilibrium, the best-fitting model that explained the familial aggregation and age at diagnosis was a rare autosomal dominant susceptibility gene, and this model fitted best when probands were diagnosed at <60 years of age. The model predicts that the frequency of the susceptibility gene in the population is .006 and that the risk of prostate cancer by age 85 years is 89% among carriers of the gene and 3% among noncarriers. A strength of our study is its large size, such that genetic models could be fitted within strata defined by the age of the proband. Although the autosomal dominant model was consistently the best model, the parameter estimates differed somewhat (P=.03) across the different age groups, suggesting genetic heterogeneity. Additional evidence that the hereditary basis of prostate cancer is likely to be genetically complex was provided by the following: (1) there was a significantly elevated age-adjusted risk of prostate cancer among brothers of probands, compared with their fathers (relative risk 1.5 [95% confidence interval 1.4-1.7]); (2) the autosomal dominant model predicted an excess of homozygotes, over that predicted by Hardy-Weinberg equilibrium; and (3) the model-predicted risk of prostate cancer among relatives was inadequate when probands were diagnosed at age >=70 years. 相似文献
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