A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus.

White, A.; Tomfohrde, J.; Stewart, Elizabeth A.; Barnes, R. Bowling; Paslier, Denis Le; Weissenbach, Jean; Cavalli-Sforza, Luca; Farrer, Lindsay A.; Bowcock, Anne M.

doi:10.1073/pnas.90.21.10105

Cited by 10 publications

(5 citation statements)

References 26 publications

(15 reference statements)

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“…It was about 850 kb in length. This region encompassed a recombination cold spot (White et al 1993). Using formula (1), we calculated that p.R778L may have originated 220 generations ago.…”

Section: Resultsmentioning

confidence: 99%

“…It is assumed that the disease allele p.R778L is rare enough to insure that an inbred affected has received two identical by descent copies, and not by chance. The PCR was performed using previously published primers (White et al 1993) and the same thermal condition stated in the part of haplotype analysis. h 0 is the length (in Morgans) of the whole chromosome where the disease locus maps.…”

Section: Haplotype Analysismentioning

confidence: 99%

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Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity

et al. 2007

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Wilson disease (WD), an autosomal recessive disorder of copper transport, is the most common inherited liver disorder in Hong Kong Chinese. This was the first local study to elucidate the molecular basis and establish an effective DNA-based diagnostic protocol. The ATP7B genes of 65 patients were amplified by polymerase chain reaction (PCR) and sequenced. Haplotype analysis was performed using D13S301, D13S314, and D13S316. The p.L770L/p.R778L status in 660 subjects was determined to estimate WD prevalence. Allele age of p.R778L was determined by the smallest homozygosity region between D13S301 and D13S270. We identified 42 different mutations with 17 being novel. p.R778L (17.3%) was the most prevalent. Exons 2, 8, 12, 13, and 16 harbored 70% mutations. Thirty-two haplotypes were associated with WD chromosomes. The estimated prevalence rate was 1 in 5,400.

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“…It was about 850 kb in length. This region encompassed a recombination cold spot (White et al 1993). Using formula (1), we calculated that p.R778L may have originated 220 generations ago.…”

Section: Resultsmentioning

confidence: 99%

Section: Haplotype Analysismentioning

confidence: 99%

Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity

et al. 2007

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“…The order of markers presented in Fig. 4 is based on the physical map established at the Third International Workshop on Human Chromosome 13 Mapping (58) and on other maps of the 13q14 region (4,29,30,40,44,59). Marker placement around the proposed R/G-band boundary also depended on the analysis of two nonoverlapping P1/PAC/BAC contigs established in this chromosomal region around STSs D13S298 and D13S137 (Fig.…”

Section: Resultsmentioning

confidence: 99%

High-Resolution Analysis of DNA Replication Domain Organization across an R/G-Band Boundary

Strehl

LaSalle

Lalande

1997

Molecular and Cellular Biology

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Establishing how mammalian chromosome replication is regulated and how groups of replication origins are organized into replication bands will significantly increase our understanding of chromosome organization. Replication time bands in mammalian chromosomes show overall congruency with structural R-and Gbanding patterns as revealed by different chromosome banding techniques. Thus, chromosome bands reflect variations in the longitudinal structure and function of the chromosome, but little is known about the structural basis of the metaphase chromosome banding pattern. At the microscopic level, both structural R and G bands and replication bands occupy discrete domains along chromosomes, suggesting separation by distinct boundaries. The purpose of this study was to determine replication timing differences encompassing a boundary between differentially replicating chromosomal bands. Using competitive PCR on replicated DNA from flow-sorted cell cycle fractions, we have analyzed the replication timing of markers spanning roughly 5 Mb of human chromosome 13q14.3/q21.1. This is only the second report of high-resolution analysis of replication timing differences across an R/G-band boundary. In contrast to previous work, however, we find that band boundaries are defined by a gradient in replication timing rather than by a sharp boundary separating R and G bands into functionally distinct chromatin compartments. These findings indicate that topographical band boundaries are not defined by specific sequences or structures.Human metaphase chromosomes can be cytogenetically identified by a distinctive banding pattern that is achieved by different staining techniques. Chromosome banding using DNA-specific stains such as Giemsa and quinacrine was first described almost 30 years ago (42), and the most common banding types are now referred to as Giemsa (G) bands and reverse (R) bands. Despite significant advances in staining techniques, there has been little progress in understanding the underlying chromosomal structures responsible for the banding phenomenon. R bands are characterized by early replication, high gene and CpG island density, and localization of a large number of both housekeeping and tissue-specific genes, and they are enriched for short interspersed repetitive elements. G bands are late replicating, contain a low number of tissue-specific genes, and are enriched for long interspersed repetitive elements (5,6,11,19,20,31,32). These general properties of R and G bands define them as distinct structural and functional units, suggesting the presence of discrete topographical boundaries. However, at higher levels of band resolution, it seems to be increasingly difficult to define narrow chromosome band boundaries, and the potential to correlate specific bands with specific functional sequences seems unlikely (19). Thus, to understand how the genome is organized in alternating chromosome bands and how boundaries between them are established, it is important to analyze functional differences between bands at the mole...

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“…It is located on chromosome 13 (13q14.3-q21.1) and consists of 21 exons, which span a DNA region of approximately 100 kb. The ATP7B gene encodes 1465-amino acid membrane protein [ 13 , 15 , 16 ] that consists of six metal-binding domains, eight transmembrane segments, an ATP-binding domain typical of copper ATPases with a P-domain, an N-domain, and an A-domain with the TGE sequence motif [ 17 - 19 ]. ATP7B is a transporter in the copper secretory pathway that delivers copper for incorporation into apoceruloplasmin and excretion into the bile [ 6 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations

Ling

et al. 2011

BMC Med Genet

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BackgroundWilson's disease (WND) is a rare autosomal recessive disorder. Here we have evaluated 62 WND cases (58 probands) from the Chinese Han population to expand our knowledge of ATP7B mutations and to more completely characterize WND in China.MethodsThe coding and promoter regions of the ATP7B gene were analyzed by direct sequencing in 62 Chinese patients (58 probands) with WND (male, n = 37; female, n = 25; age range, 2 ~ 61 years old).ResultsNeurologic manifestations were associated with older age at diagnosis (p < 0.0001) and longer diagnostic delay (p < 0.0001). Age at diagnosis was also correlated with urinary copper concentration (r = 0.58, p < 0.001). Forty different mutations, including 14 novel mutations, were identified in these patients. Common mutations included p.Arg778Leu (31.9%) and p.Pro992Leu (11.2%). Homozygous p.Arg778Leu and nonsense mutation/frameshift mutations were more often associated with primary hepatic manifestations (p = 0.0286 and p = 0.0383, respectively) and higher alanine transaminase levels at diagnosis (p = 0.0361 and p = 0.0047, respectively). Nonsense mutation/frameshift mutations were also associated with lower serum ceruloplasmin (p = 0.0065).ConclusionsWe identified 14 novel mutations and found that the spectrum of mutations of ATP7B in China is quite distinct from that of Western countries. The mutation type plays a role in predicting clinical manifestations. Genetic testing is a valuable tool to detect WND in young children, especially in patients younger than 8 years old. Four exons (8, 12, 13, and 16) and two mutations (p.Arg778Leu, p.Pro992Leu) should be considered high priority for cost-effective testing in China.

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A 4.5-megabase yeast artificial chromosome contig from human chromosome 13q14.3 ordering 9 polymorphic microsatellites (22 sequence-tagged sites) tightly linked to the Wilson disease locus.

Cited by 10 publications

References 26 publications

Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity

Mutational analysis of 65 Wilson disease patients in Hong Kong Chinese: Identification of 17 novel mutations and its genetic heterogeneity

High-Resolution Analysis of DNA Replication Domain Organization across an R/G-Band Boundary

Clinical and molecular characterization of Wilson's disease in China: identification of 14 novel mutations

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