24,043 research outputs found
Statistical and genetic-aspects of quality-control for DNA identification
No full textQuality control for likelihood ratio (LR) tests on restriction fragment length polymorphisms (RFLPs) and polymerase chain reaction (PCR) markers is provided by the 4N6 program. Examples are given for tests of exclusion, coincidence, and kinship that should be used routinely in validation of DNA profiling. They confirm that ''in a knowledgeable court DNA profiling is no longer exposed to risk of illogical presentation, blind acceptance or arbitrary rejection'' (N. E. Morton, fur: J. Hum. Genet. 1993, I, 172-179). However, they remain to be implemented in national systems of quality control. There can be no effective quality control until attempts to fudge gene frequencies in order to retain the Hardy-Weinberg assumption (recommended by the National Research Council) are abandoned in favour of the population genetic approach that takes gene frequencies from a real population and uses kinship to express genotype probabilities. Since an expert witness cannot know the identity of the culprit, he is obliged to consider multiple hypotheses without usurping the prerogative of the court to favour one of them on the basis of other evidence. It remains to be seen whether the new NRC Committee (and more importantly the international community of forensic scientists) will adopt this fundamental principle, which is especially important in populations like India with preferential endogamy and consanguineous marriages. Alternative procedures and the causes, effects, and remedies of four types of error are also considere
Nonparametric tests for linkage with dependent sib pairs
No full textSib pair tests for linkage to a quantitative trait or affection status are examined by simulation. A sibship of size s contributes only s – 1 independent sib pairs but all s(s – 1)/2 pairs are needed for an efficient test. Redundancy increases with sibship size. Using simulated data on the null hypothesis of no linkage, we have considered equal and unequal weights. Unequal weights lose power as measured by the equivalent number of observations, and goodness of fit to the theoretical distribution is degraded. The Fisher z(r) test with equally weighted pairs is more reliable than any t(r) test based on conjectured degrees of freedom, but significance levels must be established by simulation if the number of pairs is small or redundancy is large. An approach to parametric analysis through nuisance parameters is discusse
Counting algorithms for linkage
No full textThe Lander-Green algorithm is algebraically different from the EM algorithm that maximizes likelihood. In our experience the numerical difference is very small. Since computations are no easier or convergence faster for the Lander–Green algorithm, there is no reason to prefer it to EM. As suggested by Green (personal communication), layering is advantageous. Occasional updating of the information weights might also be considered to accelerate mapping
Mapping a gene for rheumatoid arthritis on chromosome 18q21
No full textAlthough single chi-square analysis of the North American Rheumatoid Arthritis Consortium (NARAC) data identifies many single-nucleotide polymorphisms (SNPs) with p-values less than 0.05, none remain significant after Bonferroni correction. In contrast, CHROMSCAN evades heavy Bonferroni correction and auto-correlation between SNPs by using composite likelihood to model association across all markers in a region and permutation to assess significance. Analysis by CHROMSCAN identifies a 36-kb interval that includes the most significant SNP (msSNP) observed in a 10-Mb target suggested by linkage. Unexpectedly, stratification by gender and age of onset shows that association evidence comes almost entirely from females with age of onset less than 40. Combining evidence from a meta-analysis of linkage studies and three subsets of the NARAC data provides significant evidence for a determinant of rheumatoid arthritis in a 36-kb interval and illustrates the principle that estimates of location and its information are more powerful than estimates of p-values alone
Does haplotype diversity predict power for positional cloning?
No full textMeeting abstract number:261
Combined segregation and linkage analysis of Graves-disease with a thyroid autoantibody diathesis
No full textCombined segregation and linkage analysis is a powerful technique for modeling linkage to diseases whose etiology is more complex than the effect of a well-described single genetic locus and for investigating the influence of single genes on various aspects of the disease phenotype. Graves disease is familial and is associated with human leukocyte antigen (HLA) allele DR3. Probands with Graves disease, as well as close relatives, have raised levels of thyroid autoantibodies. This phenotypic information additional to affection status may be considered by the computer program COMDS for combined segregation and linkage analysis, when normals are classified into diathesis classes of increasing thyroid autoantibody titer. The ordinal model considers the cumulative odds of lying in successive classes, and a single additional parameter is introduced for each gene modeled. Distributional assumptions are avoided by providing estimates of the population frequencies of each class. Evidence for linkage was increased by considering the thyroid autoantibody diathesis and by testing two-locus models. The analysis revealed evidence for linkage to HLA-DR when the strong coupling of the linked locus to allele DR3 was considered (led score of 6.6). Linkage analysis of the residual variation revealed no evidence of linkage to Gm, but a suggestion of linkage to Km
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