Abstract:
:The genes for two copper-transporting ATPases, ATP7A and ATP7B, are defective in the heritable disorders of copper imbalance, Menkes disease (MNK) and Wilson disease (WND), respectively. A comparison of the two proteins shows extensive conservation in the signature domains, with amino acid identities outside of the conserved domains being limited. The mutation spectra of MNK and WND were compared to confirm and refine further regions critical for normal function. Mutations were found to be relatively widespread; however, the majority was concentrated within defined functional domains and membrane-spanning segments, reinforcing the importance of these regions for protein function. Of the total published point mutations in ATP7A, 23.0% are splice-site, 20.7% nonsense, 17.2% missense, and 39.1% small insertions/deletions. There is a high prevalence (58.2%) of missense mutations in ATP7B. For the other mutations in ATP7B, 7.4% are splice-site, 7.4% nonsense, and 27.0% small insertions/deletions. A region of possible importance is the intervening sequence between the last copper-binding domain and the first transmembrane helix, as this region has a high percentage of MNK mutations. Similarly, the region containing the ATP-binding domain has 24.6% of all WND mutations. The study of mutation locations is useful for defining critical regions or residues and for efficient molecular diagnosis.
journal_name
Hum Genetjournal_title
Human geneticsauthors
Hsi G,Cox DWdoi
10.1007/s00439-003-1045-ykeywords:
subject
Has Abstractpub_date
2004-01-01 00:00:00pages
165-72issue
2eissn
0340-6717issn
1432-1203journal_volume
114pub_type
杂志文章相关文献
HUMAN GENETICS文献大全abstract::Leprosy is caused by infection with Mycobacterium leprae and is classified clinically into paucibacillary (PB) or multibacillary (MB) subtypes based on the number of skin lesions and the bacillary index detected in skin smears. We previously identified a major PB susceptibility locus on chromosome region 10p13 in Viet...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-014-1430-8
更新日期:2014-07-01 00:00:00
abstract::The authors report the results of a genetic analysis performed in 34 neurofibromatosis type 1 (NF1) Italian families using five loci tightly linked to NF1: D17S33, D17S82, D17S83, D17S37, and D17S36. A two-point linkage analysis was performed with the LINKAGE and the CRI-MAP programs. The map of the region was constru...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF01213101
更新日期:1991-05-01 00:00:00
abstract::Quantitative red cell adenylate kinase (AK-1) assay has been used in 8 patients with partial duplication or deletion of chromosome 9 in an attempt to find the precise intrachromosomal location of the structural gene locus. All regions of chromosome 9 are represented in abnormal dosage in at least one patient. A 43% in...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284432
更新日期:1976-09-10 00:00:00
abstract::Eight polymorphic restriction enzyme sites at the phenylalanine hydroxylase (PAH) locus were analyzed from the parental chromosomes in 33 Danish nuclear families with at least one phenylketonuric (PKU) child. Determination of haplotypes of 66 normal chromosomes and 66 chromosomes bearing mutant allele(s) demonstrated ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00283048
更新日期:1987-05-01 00:00:00
abstract::Our recent genome-wide association study (GWAS) had discovered a new locus at 8p23 (rs2738048) associated with IgA nephropathy (IgAN) in Chinese Han patients, implicating the DEFA gene family within this locus as susceptibility genes. However, it is still unknown whether there are additional variations within these ge...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-014-1464-y
更新日期:2014-10-01 00:00:00
abstract::The two human proteins with a VPS10 domain, SorLA and sortilin, both bind neuropeptides. Searching for other VPS10-domain proteins in the database revealed three new putative human neuropeptide receptors. The new receptors were designated SorCS1, SorCS2 and SorCS3, due to their identical domain composition, which, exc...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390100504
更新日期:2001-06-01 00:00:00
abstract::We report clinical and molecular findings in 15 Japanese mosaic females with r(X) chromosomes, 45,X/46,X,r(X), confirmed by fluorescence in situ hybridization (FISH) analysis for DXZ1 and whole X chromosome painting. Cases 1-3, 5-7, and 11-13 had mental retardation (MR), the remaining cases being free from MR. FISH an...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000377
更新日期:2000-11-01 00:00:00
abstract::High hyperopia is a common and severe form of refractive error. Genetic factors play important roles in the development of high hyperopia but the exact gene responsible for this condition is mostly unknown. We identified a large Chinese family with autosomal dominant high hyperopia. A genome-wide linkage scan mapped t...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-019-02039-z
更新日期:2019-10-01 00:00:00
abstract::A new case of "free" trisomy for the short arm of No. 9 chromosome identified by Giemsa staining and "Giemsa-11 technique" is reported. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284440
更新日期:1976-09-10 00:00:00
abstract::The frequencies of base-line and Mitomycin-C (MMC) induced sister chromatid exchanges (SCE) were surveyed in four inbred strains of mice. In contrast to the C57Bl/6J, CBA/J, and A/J strains where frequencies of SCE increased linearly with increasing dose of MMC, levels of SCE were significantly lower in AKR/J mice at ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278870
更新日期:1978-02-23 00:00:00
abstract::Congenital heart disease (CHD) affects over 40% of Down syndrome (DS) patients. The region proposed to contain the gene(s) for DS CHD has been restricted to 21q22.2-22.3, from D21S55 to MX1. The identification and functional characterization of the genes mapping to this region is a necessary step to understand the pat...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050693
更新日期:1998-03-01 00:00:00
abstract::An analysis of 11 I Alu insertion polymorphisms (ACE, TPA25, PV92, APO, FXIIIB, D1, A25, B65, HS2.43, HS3.23, and HS4.65) has been performed in several NW African (Northern, Western, and Southeastern Moroccans, Saharawi; Algerians; Tunisians) and Iberian (Basques, Catalans, and Andalusians) populations. Genetic distan...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000370
更新日期:2000-10-01 00:00:00
abstract::In situ hybridization of tritiated cDNA probes for the gene for the B subunit of coagulation factor XIII localized the F13B locus to bands q31-q32.1 on human chromosome 1 and perhaps more precisely to sub-bands 1q31.2 or 1q31.3. Restriction fragment length polymorphisms (RFLPs) were detected with BglII, EcoRI and XbaI...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00293893
更新日期:1989-01-01 00:00:00
abstract::Assigning a pathogenic role to mitochondrial DNA (mtDNA) variants and unveiling the potential involvement of the mitochondrial genome in diseases are challenging tasks in human medicine. Assuming that rare variants are more likely to be damaging, we designed a phylogeny-based prioritization workflow to obtain a reliab...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-015-1615-9
更新日期:2016-01-01 00:00:00
abstract::Published data on the association between FAS -1,377 G/A polymorphism and cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. A total of 17 studies including 10,564 cases and 12,075 controls were involved in this meta-analysis. Overall, significantly el...
journal_title:Human genetics
pub_type: 杂志文章,meta分析
doi:10.1007/s00439-009-0639-4
更新日期:2009-05-01 00:00:00
abstract::The hyperinsulinism-hyperammonemia syndrome (HHS) has been shown to result from 'gain-of-function' mutations of the glutamate dehydrogenase (GlDH) gene, GLUD1. In the original report, all mutations were found in a narrow range of 27 base pairs within exons 11 and 12 which predicted an effect on the presumed allosteric...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390000432
更新日期:2001-01-01 00:00:00
abstract::Distal hereditary motor neuropathies predominantly affect the motor neurons of the peripheral nervous system leading to chronic disability. Using whole genome sequencing (WGS) we have identified a novel structural variation (SV) within the distal hereditary motor neuropathy locus on chromosome 7q34-q36.2 (DHMN1). The ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-016-1720-4
更新日期:2016-11-01 00:00:00
abstract::A neonate with clinical features of the 11q23 deletion syndrome was apparently mosaic with the dominant cell line showing deletion of the chromosomal segment 11q23.3 to 11qter. The presence of a few lymphocytes with a normal karyotype indicates post-zygotic deletion of chromosome 11. The mother and brother of the prop...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00284923
更新日期:1987-06-01 00:00:00
abstract::The X chromosomes of individuals with isolated steroid sulphatase deficiency (X-linked ichthyosis) from ten families were studied by flow karyotype analysis. In four of the families, a small but significant reduction in the relative fluorescence of the X chromosome was detected consistent with a deletion ranging from ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00291709
更新日期:1988-05-01 00:00:00
abstract::This study reports the characterization of 60% of low density lipoprotein receptor (LDLR) gene mutations in 150 unrelated Greek familial hypercholesterolaemia (FH) heterozygous children by the analysis of six LDLR gene mutations. The linkage disequilibrium of two polymorphic microsatellites (D19S394 and D19S221) flank...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004390050703
更新日期:1998-03-01 00:00:00
abstract::We have studied the genetic linkage of two markers, the apolipoprotein C1 (APOC1) gene and a cytochrome P450 (CYP2A) gene, in relation to the gene for myotonic dystrophy (DM). A peak lod score of 9.29 at 2 cM was observed for APOC1-DM, with a lod score of 8.55 at 4 cM for CYP2A-DM. These two markers also show close li...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00206751
更新日期:1990-08-01 00:00:00
abstract::An 8-month-old female child with the 9p- karyotype: 46,XX,del(9) (p22) is presented, being the first case from among Oriental people. She has many clinical features similar to those described in Caucasian cases. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00295813
更新日期:1977-08-31 00:00:00
abstract::Two major obstetric diseases, preeclampsia (PE), a pregnancy-induced endothelial dysfunction leading to hypertension and proteinuria, and intra-uterine growth-restriction (IUGR), a failure of the fetus to acquire its normal growth, are generally triggered by placental dysfunction. Many studies have evaluated gene expr...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-020-02248-x
更新日期:2021-01-12 00:00:00
abstract::A reliable technique for staining human chromosomal nucleolar organizers (NOR's) with silver solutions is described. The NOR's can be selectively stained dark brown by silver solutions leaving the chromosome arms unstained and available for counterstaining with orcein or Giemsa dyes. Unequivocal identification of chro...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00278889
更新日期:1976-10-28 00:00:00
abstract::Unraveling the causes and pathomechanisms of progressive disorders is essential for the development of therapeutic strategies. Here, we identified heterozygous pathogenic missense variants of LMX1A in two families of Dutch origin with progressive nonsyndromic hearing impairment (HI), using whole exome sequencing. One ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-018-1880-5
更新日期:2018-05-01 00:00:00
abstract::A retrospective study of 200 missed abortions was performed to determine whether morphological criteria alone are sufficient to ascertain a chromosomal aetiology. Placental changes were classified into five morphological and four morphometric groups, according to the severity of alterations, and were then correlated w...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00274002
更新日期:1989-07-01 00:00:00
abstract::A highly polymorphic CA repeat was identified in a cosmid containing the 5' end of the NF2 tumour suppressor gene. This marker has proved useful in presymptomatic diagnosis in affected families. ...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00209494
更新日期:1995-06-01 00:00:00
abstract::A simple and rapid technique is described whereby the nucleolus organizer regions (NORs) of human chromosomes can be differentially stained with silver. This staining is followed by trypsin-Giemsa banding on the same metaphase chromosomes. The metaphases simultaneously exhibit silver-stained NORs and G bands, allowing...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/BF00396478
更新日期:1978-07-12 00:00:00
abstract::Mitochondrial DNA (mtDNA) haplogroups are valuable for investigations in forensic science, molecular anthropology, and human genetics. In this study, we developed a custom panel of 61 mtDNA markers for high-throughput classification of European, African, and Native American/Asian mitochondrial haplogroup lineages. Usi...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s00439-014-1421-9
更新日期:2014-07-01 00:00:00
abstract::The neurofibromatosis type 1 (NF1) gene located at 17q 11.2 contains 60 exons and spans 350 kb of genomic DNA. Mutation analysis has been hampered by the large size of the gene, the high rate of new mutations, a lack of mutational clustering and the presence of numerous homologous loci. Mutation detection methods base...
journal_title:Human genetics
pub_type: 杂志文章
doi:10.1007/s004399900135
更新日期:1999-10-01 00:00:00