Abstract：
:Pelizaeus-Merzbacher disease (PMD) is an X-linked dysmyelinating disorder caused by abnormalities in the proteolipid protein (PLP) gene, which is essential for oligodendrocyte differentiation and CNS myelin formation. Although linkage analysis has shown the homogeneity at the PLP locus in patients with PMD, exonic mutations in the PLP gene have been identified in only 10%-25% of all cases, which suggests the presence of other genetic aberrations, including gene duplication. In this study, we examined five families with PMD not carrying exonic mutations in PLP gene, using comparative multiplex PCR (CM-PCR) as a semiquantitative assay of gene dosage. PLP gene duplications were identified in four families by CM-PCR and confirmed in three families by densitometric RFLP analysis. Because a homologous myelin protein gene, PMP22, is duplicated in the majority of patients with Charcot-Marie-Tooth 1A, PLP gene overdosage may be a important genetic abnormality in PMD and affect myelin formation.
journal_name
Am J Hum Genetjournal_title
American journal of human geneticsauthors
Inoue K,Osaka H,Sugiyama N,Kawanishi C,Onishi H,Nezu A,Kimura K,Yamada Y,Kosaka Ksubject
Has Abstractpub_date
1996-07-01 00:00:00pages
32-9issue
1eissn
0002-9297issn
1537-6605journal_volume
59pub_type
杂志文章abstract：:Supernumerary marker chromosomes (SMCs) are common, but their molecular content and mechanism of origin are often not precisely characterized. We analyzed all centromere regions to identify the junction between the unique chromosome arm and the pericentromeric repeats. A molecular-ruler clone panel for each chromosome...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2007.10.013
更新日期：2008-02-01 00:00:00
abstract：:Association studies are one of the major strategies for identifying genetic factors underlying complex traits. In samples of related individuals, conventional statistical procedures are not valid for testing association, and maximum likelihood (ML) methods have to be used, but they are computationally demanding and ar...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/513895
更新日期：1997-07-01 00:00:00
abstract：:Mitochondrial genetics is complicated by heteroplasmy, or mutant load, which may be from 1%-99%, and thus may produce a gene dosage-type effect. Limited data are available for genotype/phenotype correlations in disorders caused by mtDNA mutations; therefore, prenatal diagnosis for mtDNA mutations has been hindered by ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302488
更新日期：1999-08-01 00:00:00
abstract：:The debrisoquine/sparteine polymorphism is associated with a clinically important genetic deficiency of oxidative drug metabolism. From 5% to 10% of Caucasians designated as poor metabolizers (PMs) of the debrisoquine/sparteine polymorphism have a severely impaired capacity to metabolize more than 25 therapeutically u...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-05-01 00:00:00
abstract：:Recently, a new locus (PARK8) for autosomal dominant parkinsonism has been identified in one large Japanese family. Linkage has been shown to a 16-cM centromeric region of chromosome 12, between markers D12S1631 and D12S339. We tested 21 white families with Parkinson disease and an inheritance pattern compatible with ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/380647
更新日期：2004-01-01 00:00:00
abstract：:The extent to which variants in the protein-coding sequence of genes contribute to risk of rheumatoid arthritis (RA) is unknown. In this study, we addressed this issue by deep exon sequencing and large-scale genotyping of 25 biological candidate genes located within RA risk loci discovered by genome-wide association s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2012.11.012
更新日期：2013-01-10 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：: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：:ATM, the gene that is mutated in ataxia-telangiectasia, is associated with cerebellar degeneration, abnormal proliferation of small blood vessels, and cancer. These clinically important manifestations have stimulated interest in defining the sequence variation in the ATM gene. Therefore, we undertook a comprehensive s...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/321296
更新日期：2001-08-01 00:00:00
abstract：:The introduction of stochastic methods in pedigree analysis has enabled geneticists to tackle computations intractable by standard deterministic methods. Until now these stochastic techniques have worked by running a Markov chain on the set of genetic descent states of a pedigree. Each descent state specifies the path...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1996-06-01 00:00:00
abstract：:The lysosomal hydrolase alpha-L-iduronidase (IDUA) is one of the enzymes in the metabolic pathway responsible for the degradation of the glycosaminoglycans heparan sulfate and dermatan sulfate. In humans a deficiency of IDUA leads to the accumulation of glycosaminoglycans, resulting in the lysosomal storage disorder m...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1990-11-01 00:00:00
abstract：:The Coffin-Lowry syndrome (CLS) is an X-linked inherited disease of unknown pathogenesis characterized by severe mental retardation, typical facial and digital anomalies, and progressive skeletal deformations. Our previous linkage analysis, based on four pedigrees with the disease, suggested a localization for the CLS...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-05-01 00:00:00
abstract：:Primary microcephaly is thought to result from genetic defects of the developmental program that generates large brain hemispheres in humans. Autosomal recessive inheritance is likely in most familial cases, and four loci were recently mapped by homozygosity. We report homozygosity mapping of a new locus, MCPH5, with ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/316909
更新日期：2000-12-01 00:00:00
abstract：:Small low-density lipoprotein (LDL) particles are a genetically influenced coronary disease risk factor. Lipoprotein lipase (LpL) is a rate-limiting enzyme in the formation of LDL particles. The current study examined genetic linkage of LDL particle size to the LpL gene in five families with structural mutations in th...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302234
更新日期：1999-02-01 00:00:00
abstract：:We used whole-exome sequencing to study three individuals with a distinct condition characterized by short stature, chondrodysplasia with brachydactyly, congenital joint dislocations, cleft palate, and facial dysmorphism. Affected individuals carried homozygous missense mutations in IMPAD1, the gene coding for gPAPP, ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1016/j.ajhg.2011.04.002
更新日期：2011-05-13 00:00:00
abstract：:Pathogenetic mutations in mtDNA are found in the majority of patients with Leber hereditary optic neuropathy (LHON), and molecular genetic techniques to detect them are important for the diagnosis. A false-positive molecular genetic error has adverse consequences for the diagnosis of this maternally inherited disease....
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1993-10-01 00:00:00
abstract：:Our previous studies have revealed a higher frequency of nonpolymorphic electrophoretic variants in blood samples from Amerindians than in similar samples from Caucasians and Japanese. Our present study finds, by contrast, that the frequency of deficiency variants of 11 erythrocyte enzymes, sampled in nine Amerindian ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-05-01 00:00:00
abstract：:Benign infantile familial convulsions is an autosomal dominant disorder characterized by nonfebrile seizures, with the first attack occurring at age 3-12 mo. It is one of the rare forms of epilepsy that are inherited as monogenic Mendelian traits, thus providing a powerful tool for mapping genes involved in epileptic ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/514877
更新日期：1997-10-01 00:00:00
abstract：:It is generally accepted that the blood group subtypes A1 and A2 expressions are controlled by two different blood group N-acetylgalactosaminyl-transferases, that is, A1-enzyme and A2-enzyme, respectively, and that the two types of enzymes are governed by the allelic A1 and A2 genes. The observed frequencies of blood ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1983-11-01 00:00:00
abstract：:Although balanced translocations are among the most common human chromosomal aberrations, the constitutional t(11;22)(q23;q11) is the only known recurrent non-Robertsonian translocation. Evidence indicates that de novo formation of the t(11;22) occurs during meiosis. To test the hypothesis that spatial proximity of ch...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/507652
更新日期：2006-09-01 00:00:00
abstract：:Five X-chromosome DNA markers were typed on 261 members of three large kindreds with Alport syndrome (hereditary glomerulonephritis). Lod scores greater than 3.0 for linkage between the disease locus and two of the markers confirmed X-linked inheritance of the disease. A decreasing gradient in the estimated recombinat...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-02-01 00:00:00
abstract：:The gamete-competition model is an application of the Bradley-Terry model for ranking of sports teams. If allele i of a marker locus is assigned parameter taui>0, then the probability that a parent with heterozygous genotype i/j transmits allele i is Pr(i/j-->)=tau(i)/(tau(i) + tau(j). Mendelian segregation correspond...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/302826
更新日期：2000-03-01 00:00:00
abstract：:Hereditary fructose intolerance (HFI) is a potentially fatal autosomal recessive disease of carbohydrate metabolism. HFI patients exhibit a deficiency of fructose 1-phosphate aldolase (aldolase B), the isozyme expressed in tissues that metabolize fructose. The eight protein-coding exons, including splicing signals, of...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1991-11-01 00:00:00
abstract：:X-linked ichthyosis (XLI) is an inborn error of metabolism caused by steroid sulfatase (STS) deficiency. In more than 80% of XLI patients the enzyme deficiency is due to large deletions involving the entire STS gene and flanking sequences. However, some patients with the classical XLI phenotype and complete STS defici...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:A genetical model is found to provide a good fit to family data on vitiligo. The model postulates that recessive alleles at a set of four unlinked diallelic loci are involved in the causation of the disorder. Under this multiple recessive homozygosis model, for normal X affected families ascertained through the affect...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-08-01 00:00:00
abstract：:It has been observed that multiple sulfatase deficiency disorder (MSDD) fibroblasts contained from profoundly deficient to near normal amounts of arylsulfatase (ARS) A depending on the medium in which they were cultured. Our present findings show that the major factor determining the enzyme level is the pH of the medi...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1979-09-01 00:00:00
abstract：:Knowledge of the number of causative loci is necessary to estimate the power of mapping studies of complex diseases. In the present article, we reexamine a theory developed by Risch and its implications for estimating the number L of causative loci affecting a complex inherited disease. We first show that methods base...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：10.1086/344779
更新日期：2002-12-01 00:00:00
abstract：:Methylmalonyl CoA mutase (MCM) catalyzes an essential step in the degradation of several branch-chain amino acids and odd-chain fatty acids. Deficiency of this apoenzyme causes the mut form of methylmalonic acidemia, an often fatal disorder of organic acid metabolism. An MCM cDNA has recently been obtained from human ...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1988-06-01 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：:A recombinant DNA library enriched for portions of human chromosome 13 has been constructed from a hamster-human somatic cell hybrid that contained human chromosomes 13, 12, and 6p. A total of 733 phages were identified that contain human DNA inserts, and 46 single-copy subfragments have been derived and used as probe...
journal_title：American journal of human genetics
pub_type： 杂志文章
doi：
更新日期：1984-01-01 00:00:00
