SLDB

Speech/Language Disorders Database

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Gene / phenotype associations for TDP2

  • Click column headers to sort. Click to expand any row to see more details about the particular assertion of an association between variants of TDP2 and a particular phenotypic variable.
  • Click the Pubmed IDs in the last column to link out to the primary research article. Click the links in the last column to download the full Genotype-Phenotype record as JSON or XML formatted text.
Entrez Id Symbol Location Disorder Brief Phenotype Reference Year Download
51567 TDP2 6p22.3-6p22.1 Dyslexia Single-word reading Deffenbacher et al 2004 JSON | XML

Additional Phenotype Details: Possible measures include the single-word reading subtest of Wechsler Objective Reading Dimensions
(WORD), and the British Ability Scales (BAS) test of single-word reading.


References

Elliot CD, Murray DJ, Pearson LS (1979) The British ability scales. NFER, Slough, UK

Rust J, Golombok S, Trickey G (1993) Wechsler objective reading dimensions. Psychological Corporation, Sidcup.

Basic Study Type: Linkage and association studies

Study Cohort: - DZ and MZ twin pairs (where at least one twin had a history of reading problems) and their families
- 1,559 individuals (349 nuclear families)
- Recruited from Colorado school districts

- Linkage study used all subjects
- Association study used 114 families (those with at least one child with a phenotypic score <=2 SD below mean)

Genotyping Methods: Linkage study

"Twenty-two dinucleotide repeat markers were selected for genotyping spanning 22 Mb (22 cM) on chromosome 6p21.3 (Table 1). DNA was extracted from blood or buccal samples collected from
parents and offspring. Genotyping was carried out with multiplexed fluorescently labeled primers on an ABI 3700 DNA Analyzer (Applied Biosystems). Allele calls were made by using Genotyper software version 3.7 (Applied Biosystems), and inheritance checking was performed with Genetic Analysis System (GAS) software, version 2.0 (A. Young, Oxford University, 1993–1995). The error
function in Merlin (Abecasis et al. 2002) was used to flag potential genotyping errors for re-analysis."

Association study

"SNPs were selected from the ABI Assays-on-Demand website, which offers optimized TaqMan assays for validated SNPs. SNPs were chosen based on heterozygosity, marker spacing, and a preferential location within candidate genes. Table 2 lists the 31 SNPs that were genotyped. The selected SNPs span ten genes that cluster within ~680 kb of our linkage interval, giving an average marker density of ~21 kb. SNPs were genotyped by TaqMan assay with Fam and Vic labeled MGB probes. Polymerase chain reactions were set up according to the manufacturer’s protocol and thermocycled in T-Gradient thermo-cyclers (Biometra). Endpoint fluorescent readings and allele calling were carried out on an ABI 7000 sequence detection system (SDS) with 7000SDS software (Applied Biosystems). Inheritance and error checking of allele calls were carried out as above with GAS and Merlin, respectively."

Analysis Methods: Linkage study

- Multipoint identity-by-descent values computed using GeneHunter
- Single-point linkage analysis using SIBPAL, implemented in S.A.G.E.
- Analysis performed on all 708 sib-pairs, and on samples with severe scores (at least one sib with one score 20th percentile or lower)
- S.A.G.E. implements revised Haseman-Elston analysis (using both squared trait difference and mean-corrected trait sum)
- Multipoint analysis used non-parametric lod score in GeneHunter, DeFries-Fulker basic method in QMS2, revised H-E method in QMS2
- Significance critierion for linkage: P<=0.05 and z>=1.5

Association study

- FBAT (family-based association test) with dominant and additive models
- QTDT (Quantitative Traits Disequilibrium Test) using orthogonal (Abecasis et al 2000), Allison (1997), and Rabinowitz (1997) models
- Orthogonal and Allison tests used variance components framework modeling environmental, additive, and polygenic effects
- QTDT significance levels based on 1,000 Monte Carlo permutations
- Intermarker LD using LD (GOLD) (Abecasis and Cookson 2000)
- Founder haplotypes and recombinations using Simwalk2
- Haplotypes analyzed using GeneHunter TDT option with 4-marker sliding window
- TDT significance calculated with 1,000 permutations with perm1 option in GeneHunter
- Four-marker haplotypes showing association analyzed using FBAT on markers in isolation

Other Details: Exclusion criteria:

"Subjects with sensory deficits, neurological, or emotional problems were excluded from the sample."

Phenotypes (all quantitative)

- DISC score assessing overall reading ability.
- Component phenotypes (tests described in Gayán et al. 1999):
Phoneme awareness
Phonological decoding
Single-word reading
Orthographic coice


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51567 TDP2 6p22.3-6p22.1 Dyslexia Phonological decoding ability Deffenbacher et al 2004 JSON | XML

Additional Phenotype Details: use of rule-like letter-sound relations to derive the pronunciation of pseudowords

Basic Study Type: Linkage and association studies

Study Cohort: - DZ and MZ twin pairs (where at least one twin had a history of reading problems) and their families
- 1,559 individuals (349 nuclear families)
- Recruited from Colorado school districts

- Linkage study used all subjects
- Association study used 114 families (those with at least one child with a phenotypic score <=2 SD below mean)

Genotyping Methods: Linkage study

"Twenty-two dinucleotide repeat markers were selected for genotyping spanning 22 Mb (22 cM) on chromosome 6p21.3 (Table 1). DNA was extracted from blood or buccal samples collected from
parents and offspring. Genotyping was carried out with multiplexed fluorescently labeled primers on an ABI 3700 DNA Analyzer (Applied Biosystems). Allele calls were made by using Genotyper software version 3.7 (Applied Biosystems), and inheritance checking was performed with Genetic Analysis System (GAS) software, version 2.0 (A. Young, Oxford University, 1993–1995). The error
function in Merlin (Abecasis et al. 2002) was used to flag potential genotyping errors for re-analysis."

Association study

"SNPs were selected from the ABI Assays-on-Demand website, which offers optimized TaqMan assays for validated SNPs. SNPs were chosen based on heterozygosity, marker spacing, and a preferential location within candidate genes. Table 2 lists the 31 SNPs that were genotyped. The selected SNPs span ten genes that cluster within ~680 kb of our linkage interval, giving an average marker density of ~21 kb. SNPs were genotyped by TaqMan assay with Fam and Vic labeled MGB probes. Polymerase chain reactions were set up according to the manufacturer’s protocol and thermocycled in T-Gradient thermo-cyclers (Biometra). Endpoint fluorescent readings and allele calling were carried out on an ABI 7000 sequence detection system (SDS) with 7000SDS software (Applied Biosystems). Inheritance and error checking of allele calls were carried out as above with GAS and Merlin, respectively."

Analysis Methods: Linkage study

- Multipoint identity-by-descent values computed using GeneHunter
- Single-point linkage analysis using SIBPAL, implemented in S.A.G.E.
- Analysis performed on all 708 sib-pairs, and on samples with severe scores (at least one sib with one score 20th percentile or lower)
- S.A.G.E. implements revised Haseman-Elston analysis (using both squared trait difference and mean-corrected trait sum)
- Multipoint analysis used non-parametric lod score in GeneHunter, DeFries-Fulker basic method in QMS2, revised H-E method in QMS2
- Significance critierion for linkage: P<=0.05 and z>=1.5

Association study

- FBAT (family-based association test) with dominant and additive models
- QTDT (Quantitative Traits Disequilibrium Test) using orthogonal (Abecasis et al 2000), Allison (1997), and Rabinowitz (1997) models
- Orthogonal and Allison tests used variance components framework modeling environmental, additive, and polygenic effects
- QTDT significance levels based on 1,000 Monte Carlo permutations
- Intermarker LD using LD (GOLD) (Abecasis and Cookson 2000)
- Founder haplotypes and recombinations using Simwalk2
- Haplotypes analyzed using GeneHunter TDT option with 4-marker sliding window
- TDT significance calculated with 1,000 permutations with perm1 option in GeneHunter
- Four-marker haplotypes showing association analyzed using FBAT on markers in isolation

Other Details: Exclusion criteria:

"Subjects with sensory deficits, neurological, or emotional problems were excluded from the sample."

Phenotypes (all quantitative)

- DISC score assessing overall reading ability.
- Component phenotypes (tests described in Gayán et al. 1999):
Phoneme awareness
Phonological decoding
Single-word reading
Orthographic coice


Comments


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51567 TDP2 6p22.3-6p22.1 Dyslexia Orthographic coding Deffenbacher et al 2004 JSON | XML

Additional Phenotype Details: May be assessed by a forced word choice test as in Olson et al 1994, requiring "(identification of a correctly spelt word from two phonologically equivalent options, e.g. rane vs rain" (Newbury et al 2011).

Basic Study Type: Linkage and association studies

Study Cohort: - DZ and MZ twin pairs (where at least one twin had a history of reading problems) and their families
- 1,559 individuals (349 nuclear families)
- Recruited from Colorado school districts

- Linkage study used all subjects
- Association study used 114 families (those with at least one child with a phenotypic score <=2 SD below mean)

Genotyping Methods: Linkage study

"Twenty-two dinucleotide repeat markers were selected for genotyping spanning 22 Mb (22 cM) on chromosome 6p21.3 (Table 1). DNA was extracted from blood or buccal samples collected from
parents and offspring. Genotyping was carried out with multiplexed fluorescently labeled primers on an ABI 3700 DNA Analyzer (Applied Biosystems). Allele calls were made by using Genotyper software version 3.7 (Applied Biosystems), and inheritance checking was performed with Genetic Analysis System (GAS) software, version 2.0 (A. Young, Oxford University, 1993–1995). The error
function in Merlin (Abecasis et al. 2002) was used to flag potential genotyping errors for re-analysis."

Association study

"SNPs were selected from the ABI Assays-on-Demand website, which offers optimized TaqMan assays for validated SNPs. SNPs were chosen based on heterozygosity, marker spacing, and a preferential location within candidate genes. Table 2 lists the 31 SNPs that were genotyped. The selected SNPs span ten genes that cluster within ~680 kb of our linkage interval, giving an average marker density of ~21 kb. SNPs were genotyped by TaqMan assay with Fam and Vic labeled MGB probes. Polymerase chain reactions were set up according to the manufacturer’s protocol and thermocycled in T-Gradient thermo-cyclers (Biometra). Endpoint fluorescent readings and allele calling were carried out on an ABI 7000 sequence detection system (SDS) with 7000SDS software (Applied Biosystems). Inheritance and error checking of allele calls were carried out as above with GAS and Merlin, respectively."

Analysis Methods: Linkage study

- Multipoint identity-by-descent values computed using GeneHunter
- Single-point linkage analysis using SIBPAL, implemented in S.A.G.E.
- Analysis performed on all 708 sib-pairs, and on samples with severe scores (at least one sib with one score 20th percentile or lower)
- S.A.G.E. implements revised Haseman-Elston analysis (using both squared trait difference and mean-corrected trait sum)
- Multipoint analysis used non-parametric lod score in GeneHunter, DeFries-Fulker basic method in QMS2, revised H-E method in QMS2
- Significance critierion for linkage: P<=0.05 and z>=1.5

Association study

- FBAT (family-based association test) with dominant and additive models
- QTDT (Quantitative Traits Disequilibrium Test) using orthogonal (Abecasis et al 2000), Allison (1997), and Rabinowitz (1997) models
- Orthogonal and Allison tests used variance components framework modeling environmental, additive, and polygenic effects
- QTDT significance levels based on 1,000 Monte Carlo permutations
- Intermarker LD using LD (GOLD) (Abecasis and Cookson 2000)
- Founder haplotypes and recombinations using Simwalk2
- Haplotypes analyzed using GeneHunter TDT option with 4-marker sliding window
- TDT significance calculated with 1,000 permutations with perm1 option in GeneHunter
- Four-marker haplotypes showing association analyzed using FBAT on markers in isolation

Other Details: Exclusion criteria:

"Subjects with sensory deficits, neurological, or emotional problems were excluded from the sample."

Phenotypes (all quantitative)

- DISC score assessing overall reading ability.
- Component phenotypes (tests described in Gayán et al. 1999):
Phoneme awareness
Phonological decoding
Single-word reading
Orthographic coice


Comments


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51567 TDP2 6p22.3-6p22.1 Principal component reading and spelling CORE score Luciano et al 2007 JSON | XML

Additional Phenotype Details: Principal component obtained from Components of Reading Examination (CORE)

Associated Markers:
rs2143340  (P = 0.02)


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51567 TDP2 6p22.3-6p22.1 Bivariate Word Reading Luciano et al 2007 JSON | XML

Additional Phenotype Details: Cambridge and Schonell Whole-Word Reading Tests

Associated Markers:
rs2143340  (P = 0.01)


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