Abstract：
:Electrophoretic properties of eight lysosomal hydrolases and 36 nonlysosomal enzymes were investigated in cultured fibroblasts from children with the inherited storage disease mucolipidosis II (ML II); fibroblasts from a child with a related disorder, mucolipidosis III (ML III); and two obligate heterozygous cell lines from parents of a ML II child. Cell homogenates of ML II fibroblast lines showed altered mobilities for lysosomal beta-hexosaminidase, acid phosphatase2, and alpha-mannosidase and deficient activity for the esterase-A4 and lysosomal alpha-mannosidase-B electrophoretic phenotypes. Altered mobility was also detected for the nonlysosomal enzyme adenosine deaminase-d. Deficient activities of other lysosomal enzymes were observed as previously reported. In a single ML III fibroblast line, only beta-hexosaminidase showed an abnormal electrophoretic pattern suggesting a difference between these cells and ML II fibroblasts. Thirty-five nonlysosomal enzymes associated with other cellular organelles and metabolic pathways were electrophoretically normal in all mucolipidosis cell lines. Heterozygous ML II cells showed normal expression for all enzymes. Two major patterns of altered lysosomal enzymes and adenosine deaminase were demonstrated in ML II cell lines, suggesting that at least two genetic forms of this disorder may exist. Neuraminidase treatment of ML II homogenates converted altered forms of acid phosphatase2 and adenosine deaminase-d and in two ML II lines, recovered the previously undetected lysosomal alpha-mannosidase band. These results are consistent with the mucolipidosis defect(s) being associated with abnormal post-translatinal processing of multiple lysosomal enzymes and adenosine deaminase-d.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Champion MJ,Shows TBsubject
Has Abstractpub_date
1977-03-01 00:00:00pages
149-63issue
2eissn
0002-9297issn
1537-6605journal_volume
29pub_type
杂志文章abstract：:A black family with two male infants affected with the X-linked Lowe syndrome was studied. All three females in the pedigree were found to be carriers on the basis of lenticular opacities. Each female had one son. Of these, two were affected and one was unaffected. The Xg blood-group locus and the G6PD locus were dete...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1982-11-01 00:00:00
abstract：:Nondisjunction in trisomy 21 has traditionally been studied by cytogenetic heteromorphisms. Those studies assumed no crossing-over on the short arm of chromosome 21. Recently, increased accuracy of detection of the origin of nondisjunction has been demonstrated by DNA polymorphism analysis. We describe a comparative s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-09-01 00:00:00
abstract：:Premature ovarian failure (POF) is characterized by elevated gonadotropins and amenorrhea in women aged <40 years. In a Lebanese family with five sisters who received the diagnosis of POF, we established linkage to the long arm of the X chromosome (between Xq21.1 and Xq21.3.3), using whole-genome SNP typing and homozy...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/505406
更新日期：2006-07-01 00:00:00
abstract：:Split hand/split foot (SHFD) is a human developmental defect characterized by missing digits, fusion of remaining digits, and a deep median cleft in the hands and feet. Cytogenetic studies of deletions and translocations associated with this disorder have indicated that an autosomal dominant split hand/split foot locu...
journal_title：American journal of human genetics
pub_type： 杂志文章,评审
doi：
更新日期：1994-07-01 00:00:00
abstract：:We describe a new user-intense-learning experience that incorporates the teaching of clinical and research applications of human genetics in biochemistry while training first-year medical students to develop skills in computer access to the literature. Human genetics was incorporated into the biochemistry curriculum b...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-04-01 00:00:00
abstract：:Neuroblastoma is a cancer of the developing sympathetic nervous system. It is diagnosed in 600-700 children per year in the United States and accounts for 12% of pediatric cancer deaths. Despite recent advances in our understanding of this malignancy's complex genetic architecture, the contribution of rare germline va...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.07.020
更新日期：2019-09-05 00:00:00
abstract：:Little is known about the genetics of nonsyndromic intellectual disability (NSID). We hypothesized that de novo mutations (DNMs) in synaptic genes explain an important fraction of sporadic NSID cases. In order to investigate this possibility, we sequenced 197 genes encoding glutamate receptors and a large subset of th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.02.001
更新日期：2011-03-11 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
abstract：:Criteria and rules are derived for the most statistically efficient sampling of relatives of affected probands under a simple class of standard genetic models. Results show that the optimal relative type depends on the alternative hypotheses of particular interest. Thus, there is no uniformly optimal strategy, but the...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1981-11-01 00:00:00
abstract：:The opportunity raised by recombinant DNA technology to develop a linkage marker panel that spans the human genome requires cost-efficient strategies for its optimal utilization. Questions arise as to whether it is more cost-effective to convert a dimorphic restriction enzyme marker system into a highly polymorphic sy...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1986-07-01 00:00:00
abstract：:Although the use of model systems for studying the mechanism of mutations that have a large effect is common, we highlight here the ways that zebrafish-model-system studies of a gene, GRIK5, that contributes to the polygenic liability to develop eye diseases have helped to illuminate a mechanism that implicates vascul...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2019.01.017
更新日期：2019-03-07 00:00:00
abstract：:The original family with the Allan-Herndon type of X-linked mental retardation has been investigated for linkage by using DNA probes spanning the length of the X chromosome. Available for study, over 3 generations, were 13 affected males, three obligate carriers, and three normal sons of the obligate carriers. Initial...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-09-01 00:00:00
abstract：:Hirschsprung disease (HSCR) is a common congenital disorder characterized by aganglionosis of the gut. The seemingly unrelated multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder characterized by medullary thyroid carcinoma (MTC), pheochromocytoma, and hyperparathyroidism. Yet, germline mutat...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/345466
更新日期：2003-01-01 00:00:00
abstract：:Hereditary spastic paraplegia (HSP) is a genetically and clinically heterogeneous disease characterized by spasticity and weakness of the lower limbs with or without additional neurological symptoms. Although more than 70 genes and genetic loci have been implicated in HSP, many families remain genetically undiagnosed,...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2016.04.002
更新日期：2016-05-05 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：:A total of 254 affected parent-child pairs with Huntington disease (HD) and 440 parent-child pairs with CAG size in the normal range were assessed to determine the nature and frequency of intergenerational CAG changes in the HD gene. Intergenerational CAG changes are extremely rare (3/440 [0.68%]) on normal chromosome...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-08-01 00:00:00
abstract：:RNA sequencing (RNA-seq) is gaining popularity as a complementary assay to genome sequencing for precisely identifying the molecular causes of rare disorders. A powerful approach is to identify aberrant gene expression levels as potential pathogenic events. However, existing methods for detecting aberrant read counts ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2018.10.025
更新日期：2018-12-06 00:00:00
abstract：:Allan-Herndon-Dudley syndrome was among the first of the X-linked mental retardation syndromes to be described (in 1944) and among the first to be regionally mapped on the X chromosome (in 1990). Six large families with the syndrome have been identified, and linkage studies have placed the gene locus in Xq13.2. Mutati...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/431313
更新日期：2005-07-01 00:00:00
abstract：:In this paper we present linkage results from the analysis of 18 Utah breast cancer kindreds, for three 17q markers. Four kindreds had LOD scores greater than 1.0 for at least one of the marker loci. One of these kindreds has a LOD score of 6.07 with D17S579, and we believe it to be the most informative 17q family rep...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-04-01 00:00:00
abstract：:SOX6 belongs to a family of 20 SRY-related HMG-box-containing (SOX) genes that encode transcription factors controlling cell fate and differentiation in many developmental and adult processes. For SOX6, these processes include, but are not limited to, neurogenesis and skeletogenesis. Variants in half of the SOX genes ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2020.04.015
更新日期：2020-06-04 00:00:00
abstract：:The original test for the analysis of the CCG expansion at the FRAXE locus involves Southern blot analysis of HindIII digests. We show that, by using a different probe, the FRAXE mutation can be detected easily on the same EcoRI or EagI+EcoRI blots as are used for detection of FRAXA. Unexpectedly, we found that both t...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-10-01 00:00:00
abstract：:Attention-deficit hyperactivity disorder (ADHD) has been shown to be familial and heritable, in previous studies. As with most psychiatric disorders, examination of pedigrees has not revealed a consistent Mendelian mode of transmission. The response of ADHD patients to medications that inhibit the dopamine transporter...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1995-04-01 00:00:00
abstract：:Increased concentrations of total sulfated mucopolysaccharides (MPS), threefold, and hyaluronic acid (HA), 10-fold, were found in ML IV fibroblast extracts when compared to normal controls. Such accumulations altered the distribution of MPS:HA comprised 70% of total MPS in ML IV but only 30% in control cells. Intracel...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1977-11-01 00:00:00
abstract：:Linkage of Alzheimer disease (AD) to DNA markers on chromosomes 14, 19, and 21 was studied in 10 families in which the disease was apparently inherited as an autosomal dominant trait. Families were derived from a Dutch population-based epidemiologic study of early-onset AD. Although in all probands the onset of AD was...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1994-10-01 00:00:00
abstract：:Chiasma frequency data on 183 males were subjected to an analysis of covariance. There appeared to be little or no linear trend in chiasma frequency with age. This conclusion was supported by a detailed analysis of chiasma frequencies for each autosome from 21 males. There were, however, significant differences among ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1975-05-01 00:00:00
abstract：:Pooling genome-wide association studies (GWASs) increases power but also poses methodological challenges because studies are often heterogeneous. For example, combining GWASs of related but distinct traits can provide promising directions for the discovery of loci with small but common pleiotropic effects. Classical a...
journal_title：American journal of human genetics
pub_type： 杂志文章,meta分析
doi：10.1016/j.ajhg.2012.03.015
更新日期：2012-05-04 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：:The Lowe syndrome (LS), or oculocerebrorenal syndrome, has been studied using DNA-based linkage analysis, and the findings have been correlated with the result of a thorough ophthalmologic examination. It was found that the LS gene was linked to markers in the Xq24-q26 region and that the locus DXS42 was the most clos...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1989-02-01 00:00:00
abstract：:Hyperkalemic periodic paralysis (HYPP) is an autosomal dominant muscle disease with electrophysiological abnormalities suggesting a defect in a voltage-gated sodium channel (NaCh) gene. A human NaCh gene was recently shown to cosegregate with the disease allele in a family with HYPP. Using an independent clone, we hav...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-08-01 00:00:00
abstract：:Model-free LOD-score methods are often employed to detect linkage between marker loci and common diseases, with samples of affected sib pairs. Although extensions of the basic one-disease-locus model have been proposed that allow separate inclusion of other types of affected relative pairs, discordant relative pairs, ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302662
更新日期：1999-12-01 00:00:00
