Refined Assignment of the Infantile Neuronal Ceroid Lipofuscinosis (INCL, CLN1) Locus at 1p32: Incorporation of Linkage Disequilibrium in Multipoint Analysis

Hellsten, Elina; Vesa, Jouni; Speer, Marcy C.; Mäkelä, Tomi P.; Järvelä, Irma; Alitalo, Kari; Ott, Jürg; Peltonen, Leena

doi:10.1006/geno.1993.1253

Cited by 49 publications

(27 citation statements)

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“…In such cases, most of the disease carriers should have the same marker allele in the chromosome containing the disease allele; the two loci are in linkage disequilibrium (23). Thus, in the Finnish population, linkage disequilibrium extending relatively far from the disease locus may be expected, which dramatically increases the informativeness of linkage analyses (24,25).…”

Section: Discussionmentioning

confidence: 99%

Infantile Onset Spinocerebellar Ataxia Represents an Allelic Disease Distinct from Other Hereditary Ataxias

et al. 1994

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Section: Discussionmentioning

confidence: 99%

Infantile Onset Spinocerebellar Ataxia Represents an Allelic Disease Distinct from Other Hereditary Ataxias

et al. 1994

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“…The PPT1 gene was identified as a candidate for the disorder when it was mapped to chromosome 1p32, a region known to contain the defective gene in a group of Finnish patients (3). Over 20 different mutations in the PPT1 gene have been identified in NCL patients worldwide (4).…”

Section: Nfantile Neuronal Ceroid Lipofuscinosis (Incl) Is the Mostmentioning

confidence: 99%

The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis

Bellizzi

Widom

Kemp

et al. 2000

Proc. Natl. Acad. Sci. U.S.A.

142

125

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Mutations in palmitoyl-protein thioesterase 1 (PPT1), a lysosomal enzyme that removes fatty acyl groups from cysteine residues in modified proteins, cause the fatal inherited neurodegenerative disorder infantile neuronal ceroid lipofuscinosis. The accumulation of undigested substrates leads to the formation of neuronal storage bodies that are associated with the clinical symptoms. Less severe forms of PPT1 deficiency have been found recently that are caused by a distinct set of PPT1 mutations, some of which retain a small amount of thioesterase activity. We have determined the crystal structure of PPT1 with and without bound palmitate by using multiwavelength anomalous diffraction phasing. The structure reveals an ␣͞␤-hydrolase fold with a catalytic triad composed of Ser115-His289-Asp233 and provides insights into the structural basis for the phenotypes associated with PPT1 mutations.

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“…6 The capability to model LD with haplotype frequencies has long been included in the LINKAGE package, 35 and LD was used for fine mapping many disease genes cloned in the 1980s and 1990s. 1,[3][4][5][6][7][8]10,[42][43][44] In the past decade, two other software packages have implemented joint analysis of linkage and LD: LAMP and MENDEL. However, MENDEL does not perform adequately under M Rec because it conditions disease allele frequencies on the marker alleles found on each haplotype, constraining the overall disease allele frequency.…”

Section: Methods To Be Comparedmentioning

confidence: 99%

“…Regions identified through linkage analysis often contain many genes, making identification of the disease-predisposing alleles difficult. After a finding of significant linkage, association analysis can aid in fine mapping, [1][2][3][4][5][6][7][8][9][10] as it measures the effects of recombination over many meioses that historically connect affected individuals to one another. Association mapping can be done using either families or 'unrelated' singleton individuals, while linkage analysis requires families, as it measures correlations in genotype among relatives.…”

Section: Introductionmentioning

confidence: 99%

On the statistical properties of family-based association tests in datasets containing both pedigrees and unrelated case–control samples

et al. 2011

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A common approach to genetic mapping of loci for complex diseases is to perform a genome-wide association study (GWAS) by analyzing a vast number of SNP markers in cohorts of unrelated cases and controls. A direct motivation for the case-control design is that unrelated, affected individuals can be easier to collect than large families with multiple affected persons in the Western world. Despite its higher potential power, investigators have not actively pursued family ascertainment in part because of a dearth of methods for analyzing such correlated data on a large scale. We examine the statistical properties of several commonly used family-based association tests, as to their performance using real-life mixtures of families and singletons taken from our own migraine and schizophrenia studies, as well as population-based data for a complex trait simulated with the evolutionary phenogenetic simulator, ForSim. In virtually every situation, the full likelihood-based methods in the PSEUDOMARKER program outperformed those implemented in FBAT, GENEHUNTER TDT, PLINK (family-based options), HRR/HHRR, QTDT, TRANSMIT, UNPHASED, MENDEL, and LAMP. We further show that GWAS is much more powerful when family samples are used rather than unrelateds, on a genotype-by-genotype basis.

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Refined Assignment of the Infantile Neuronal Ceroid Lipofuscinosis (INCL, CLN1) Locus at 1p32: Incorporation of Linkage Disequilibrium in Multipoint Analysis

Cited by 49 publications

References 0 publications

Infantile Onset Spinocerebellar Ataxia Represents an Allelic Disease Distinct from Other Hereditary Ataxias

Infantile Onset Spinocerebellar Ataxia Represents an Allelic Disease Distinct from Other Hereditary Ataxias

The crystal structure of palmitoyl protein thioesterase 1 and the molecular basis of infantile neuronal ceroid lipofuscinosis

On the statistical properties of family-based association tests in datasets containing both pedigrees and unrelated case–control samples

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