Abstract:
:Chromosomal aneuploidy is usually identified by cytogenetic methods. However, for some purposes it would be desirable to have an easier method of recognizing specific trisomies or monosomies. We have devised such an assay. It involves the simultaneous hybridization of two chromosome-specific DNA probes labeled with different isotopes (32P and 35S) to human chromosomal DNA immobilized on a nitrocellulose filter. The hybridization signals are then counted, and the dpm ratios between the two isotopes are determined. In this paper we show the application of this technique in sex determination, in the analysis of two human cell lines reported to have chromosome 21 monosomy, and, especially, in testing for Down syndrome.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Dahl HH,Choo KH,Danks DMsubject
Has Abstractpub_date
1988-10-01 00:00:00pages
502-10issue
4eissn
0002-9297issn
1537-6605journal_volume
43pub_type
杂志文章abstract::A reproducible and convenient method for assaying glucocerebrosidase activity using the natural substrates has been developed. From the insoluble pellet fraction of cultured skin fibroblast homogenates, released glucose was measured enzymically using hexokinase coupled with the glucose-6-phosphate dehydrogenase (G6PD)...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1980-09-01 00:00:00
abstract::While genetic causes are known for many syndromes involving developmental anomalies, a large number of individuals with overlapping phenotypes remain undiagnosed. Using exome-sequencing analysis and review of matchmaker databases, we have discovered four de novo missense variants predicted to affect the N-terminal reg...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2019.06.015
更新日期:2019-08-01 00:00:00
abstract::The first component of the mitochondrial electron-transport chain is especially complex, consisting of 19 nuclear and seven mitochondrion-encoded subunits. Accordingly, a wide range of clinical manifestations are produced by the various mutations occurring in human populations. In this study, we analyze the subunit st...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-06-01 00:00:00
abstract::Familial amyotrophic lateral sclerosis (FALS) affects 5%-10% of cases of amyotrophic lateral sclerosis (ALS) and is inherited as an autosomal dominant condition with incomplete penetrance. One-fifth of these cases of FALS are associated with mutations in copper/zinc-dependent superoxide dismutase (SOD1), but the gene ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/377156
更新日期:2003-08-01 00:00:00
abstract::Restriction-fragment-length-polymorphism analysis was used to examine a female who is segregating for Duchenne muscular dystrophy (DMD) and a deletion of the DXS164 region of the X chromosome. The segregating female has no prior family history of DMD, and she has two copies of the DXS164 region in her peripheral blood...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-08-01 00:00:00
abstract::X chromosome inactivation results in the random transcriptional silencing of one of the two X chromosomes early in female development. After random inactivation, certain deleterious X-linked mutations can create a selective disadvantage for cells in which the mutation is on the active X chromosome, leading to X inacti...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302286
更新日期:1999-03-01 00:00:00
abstract::Epigenetic modifications such as DNA methylation play a key role in gene regulation and disease susceptibility. However, little is known about the genome-wide frequency, localization, and function of methylation variation and how it is regulated by genetic and environmental factors. We utilized the Multiple Tissue Hum...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2013.10.004
更新日期:2013-11-07 00:00:00
abstract::Linkage is a phenomenon that correlates the genotypes of loci, rather than the phenotypes of one locus to the genotypes of another. It is therefore necessary to convert the observed trait phenotypes into trait-locus genotypes, which can then be analyzed for coinheritance with marker-locus genotypes. However, if the mo...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302797
更新日期:2000-03-01 00:00:00
abstract::The alkaline phosphatases comprise a multigene enzyme family that hydolyze phosphate esters and are widely distributed in nature. Three main classes have been isolated from humans, the placental, intestinal, and liver/bone/kidney forms. We have mapped the placental and intestinal alkaline phosphatase genes to 2q34-q37...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Whole-genome and exome sequence data can be cost-effectively generated for the detection of rare-variant (RV) associations in families. Causal variants that aggregate in families usually have larger effect sizes than those found in sporadic cases, so family-based designs can be a more powerful approach than population...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.12.001
更新日期:2017-02-02 00:00:00
abstract::Joubert syndrome (JBTS) is an autosomal-recessive disorder characterized by a distinctive mid-hindbrain malformation, developmental delay with hypotonia, ocular-motor apraxia, and breathing abnormalities. Although JBTS was first described more than 40 years ago in French Canadian siblings, the causal mutations have no...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2012.02.011
更新日期:2012-04-06 00:00:00
abstract::We recently reported the absence of significant linkage of phonological coding dyslexia (PCD) to chromosome 6p23-p21.3 in 79 families with at least two affected siblings, even though linkage of dyslexia to this region has been found in four other independent studies. Whereas, in our previous analyses, we used a qualit...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/302764
更新日期:2000-02-01 00:00:00
abstract::Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to e...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2018.11.002
更新日期:2019-01-03 00:00:00
abstract::The problem considered is that of estimating the age or rate of increase of a variant on the basis of the present number of replicates observed in a population. In place of previous diffusion equation analyses of age probability distributions, the likelihood for the age is studied on the basis of a discrete branching ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1976-09-01 00:00:00
abstract::Living at high altitude is one of the most difficult challenges that humans had to cope with during their evolution. Whereas several genomic studies have revealed some of the genetic bases of adaptations in Tibetan, Andean, and Ethiopian populations, relatively little evidence of convergent evolution to altitude in di...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2014.09.002
更新日期:2014-10-02 00:00:00
abstract::Case-control studies compare marker-allele distributions in affected and unaffected individuals, and significant results suggest linkage but may simply reflect population structure. For markers with m alleles (m > or = 2), a McNemar-like statistic, I, estimates the level of population association between marker and di...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1997-03-01 00:00:00
abstract::Genome regions containing multiple copies of homologous genes, such as the immunoglobulin (Ig) heavy-chain constant-region (IGHC) locus, are often unstable and give rise to duplicated and deleted haplotypes. Analysis of such processes is fundamental to understanding the mechanisms of evolution of multigene families. I...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1991-04-01 00:00:00
abstract::Autosomal dominant familial exudative vitreoretinopathy (adFEVR) is a hereditary disorder characterized by the incomplete vascularization of the peripheral retina. The primary biochemical defect in adFEVR is unknown. The adFEVR locus has tentatively been assigned to 11q by linkage studies. We report the results of an ...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-10-01 00:00:00
abstract::Ankylosing spondylitis (AS) is a common inflammatory arthritis predominantly affecting the axial skeleton. Susceptibility to the disease is thought to be oligogenic. To identify the genes involved, we have performed a genomewide scan in 185 families containing 255 affected sibling pairs. Two-point and multipoint nonpa...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/319509
更新日期:2001-04-01 00:00:00
abstract::On the basis of the known amino acid sequence of statherin, a human salivary protein, mixed synthetic oligonucleotides were synthesized and used to screen a cDNA library constructed from human parotid-gland mRNA. A cDNA clone coding for statherin was isolated from this library and has been completely sequenced. The cD...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-12-01 00:00:00
abstract::Rheumatoid arthritis (RA) is an autoimmune/inflammatory disorder with a complex genetic component. We report the first major genomewide screen of multiplex families with RA gathered in the United States. The North American Rheumatoid Arthritis Consortium, using well-defined clinical criteria, has collected 257 familie...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/319518
更新日期:2001-04-01 00:00:00
abstract::The gene for vimentin, an intermediate-filament protein, is growth regulated. We used Southern blot analysis and in situ chromosome hybridization to determine the location of the human vimentin gene. Our results show that there is only one copy of the vimentin gene and that it is located on the short arm of chromosome...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1987-10-01 00:00:00
abstract::Increased male prevalence has been repeatedly reported in several neurodevelopmental disorders (NDs), leading to the concept of a "female protective model." We investigated the molecular basis of this sex-based difference in liability and demonstrated an excess of deleterious autosomal copy-number variants (CNVs) in f...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2014.02.001
更新日期:2014-03-06 00:00:00
abstract::Curry-Jones syndrome (CJS) is a multisystem disorder characterized by patchy skin lesions, polysyndactyly, diverse cerebral malformations, unicoronal craniosynostosis, iris colobomas, microphthalmia, and intestinal malrotation with myofibromas or hamartomas. Cerebellar medulloblastoma has been described in a single af...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2016.04.007
更新日期:2016-06-02 00:00:00
abstract::The chromosome 19 apolipoprotein E/CI/CII gene cluster was examined for evidence of linkage to a familial Alzheimer disease (FAD) locus. The family groups studied were Volga German (VG), early-onset non-VG (ENVG; mean age at onset < 60 years), and late-onset families. A genetic association was observed between apolipo...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::A case of a 46,XYp- phenotypic female provided an opportunity to evaluate both sexual and somatic determinants for the Y chromosome. The patient had multiple stigmata of Turner syndrome, but normal stature. Laparotomy revealed a normal uterus and tubes, with 1.5 cm undifferentiated gonads. Serological tests for H-Y an...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1979-07-01 00:00:00
abstract::Lumbar-disc herniation (LDH), one of the most common musculoskeletal diseases, has strong genetic determinants. Recently, several genes that encode extracellular matrix (ECM) proteins in the intervertebral disc have been reported to associate with LDH. Thrombospondins (THBSs) 1 and 2 are good candidates for the LDH su...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2008.03.013
更新日期:2008-05-01 00:00:00
abstract::A mutation involving an A-to-G nucleotide replacement at position 985 of the medium-chain acyl-CoA dehydrogenase (MCAD) cDNA was found in homozygous form in 18 unrelated MCAD-deficient families and in heterozygous form in 4 families. By PCR amplification and sequencing of cDNA from a compound heterozygote, we have det...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:
更新日期:1992-01-01 00:00:00
abstract::Despite the accelerated discovery of genes associated with syndromic traits, the majority of families affected by such conditions remain undiagnosed. Here, we employed whole-exome sequencing in two unrelated consanguineous kindreds with central nervous system (CNS), cardiac, renal, and digit abnormalities. We identifi...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1016/j.ajhg.2017.02.007
更新日期:2017-04-06 00:00:00
abstract::We demonstrate that satellite III (SatIII) DNA subfamilies cloned from human acrocentric chromosomes arose in the Hominoidea superfamily. Two groups, distinguished by sequence composition, evolved nonconcurrently, with group 2 evolving 16-23 million years ago (MYA) and the more recent group 1 sequences emerging approx...
journal_title:American journal of human genetics
pub_type: 杂志文章
doi:10.1086/512132
更新日期:2007-03-01 00:00:00