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Faster sequential genetic linkage computations.

TLDR
A variety of algorithmic improvements are described, which synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.
Abstract
Linkage analysis using maximum-likelihood estimation is a powerful tool for locating genes. As available data sets have grown, the computation required for analysis has grown exponentially and become a significant impediment. Others have previously shown that parallel computation is applicable to linkage analysis and can yield order-of-magnitude improvements in speed. In this paper, we demonstrate that algorithmic modifications can also yield order-of-magnitude improvements, and sometimes much more. Using the software package LINKAGE, we describe a variety of algorithmic improvements that we have implemented, demonstrating both how these techniques are applied and their power. Experiments show that these improvements speed up the programs by an order of magnitude, on problems of moderate and large size. All improvements were made only in the combinatorial part of the code, without restoring to parallel computers. These improvements synthesize biological principles with computer science techniques, to effectively restructure the time-consuming computations in genetic linkage analysis.

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Citations
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Merlin--rapid analysis of dense genetic maps using sparse gene flow trees.

TL;DR: The multipoint engine for rapid likelihood inference (Merlin) is a computer program that uses sparse inheritance trees for pedigree analysis; it performs rapid haplotyping, genotype error detection and affected pair linkage analyses and can handle more markers than other pedigree analysis packages.
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Genetic dissection of complex traits

TL;DR: This article synthesizes the current state of the genetic dissection of complex traits--describing the methods, limitations, and recent applications to biological problems.
Journal Article

Parametric and nonparametric linkage analysis: a unified multipoint approach.

TL;DR: It is shown that NPL is robust to uncertainty about mode of inheritance, is much more powerful than commonly used nonparametric methods, and loses little power relative to parametric linkage analysis, and appears to be the method of choice for pedigree studies of complex traits.
Journal ArticleDOI

Hypogonadotropic hypogonadism due to loss of function of the KiSS1-derived peptide receptor GPR54

TL;DR: The present study shows that loss of function of GPR54 is a cause of IHH, and it identifies GPR 54 and possibly KiSS1 protein-derived peptide as playing a major and previously unsuspected role in the physiology of the gonadotropic axis.
References
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Journal ArticleDOI

Strategies for multilocus linkage analysis in humans.

TL;DR: The results show that considerable economy and efficiency can be brought to the mapping endeavor by resorting to appropriate strategies of detecting linkage and by constructing the human genetic map on a common reference panel of families.
Journal Article

Easy calculations of lod scores and genetic risks on small computers.

TL;DR: A computer program that calculates lod scores and genetic risks for a wide variety of both qualitative and quantitative genetic traits is discussed and an illustration is given of the joint use of a genetic marker, affection status, and quantitative information in counseling situations regarding Duchenne muscular dystrophy.
Journal ArticleDOI

Extensions to Pedigree Analysis

TL;DR: In this paper, a computer method for calculating recurrence under the polygenic threshold model is explained, which permits accurate risk evaluation for pedigrees of arbitrary structure and large enough size.
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