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

Nat Genet 2002 Jan 3;30(1):97-101. Epub 2001 Dec 3.

The Wellcome Trust Center for Human Genetics, University of Oxford, Oxford OX3 7BN, UK.

Efforts to find disease genes using high-density single-nucleotide polymorphism (SNP) maps will produce data sets that exceed the limitations of current computational tools. Here we describe a new, efficient method for the analysis of dense genetic maps in pedigree data that provides extremely fast solutions to common problems such as allele-sharing analyses and haplotyping. We show that sparse binary trees represent patterns of gene flow in general pedigrees in a parsimonious manner, and derive a family of related algorithms for pedigree traversal. With these trees, exact likelihood calculations can be carried out efficiently for single markers or for multiple linked markers. Using an approximate multipoint calculation that ignores the unlikely possibility of a large number of recombinants further improves speed and provides accurate solutions in dense maps with thousands of markers. Our 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.

Download full-text PDF

Source
http://www.nature.com/doifinder/10.1038/ng786
Publisher Site
http://dx.doi.org/10.1038/ng786DOI Listing
January 2002
11 Reads

Publication Analysis

Top Keywords

pedigree analysis
8
genetic maps
8
gene flow
8
dense genetic
8
analysis dense
8
markers
4
single markers
4
efficiently single
4
exact likelihood
4
likelihood calculations
4
calculations carried
4
carried efficiently
4
linked markers
4
calculation ignores
4
ignores possibility
4
possibility large
4
multipoint calculation
4
approximate multipoint
4
multiple linked
4
trees exact
4

References

(Supplied by CrossRef)

JC Mullikin et al.
Nature 2000

D Altshuler et al.
Nature 2000

GM Lathrop et al.
Am. J. Hum. Genet. 1985

L Kruglyak et al.
Am. J. Hum. Genet. 1995

JR O'Connell et al.
Nature Genet. 1995

RW Cottingham Jr et al.
Am. J. Hum. Genet. 1993

E Sobel et al.
Am. J. Hum. Genet. 1996

SC Heath et al.
Am. J. Hum. Genet. 1997

DF Gudbjartsson et al.
Nature Genet. 2000

RC Elston et al.
Hum. Hered. 1971

ES Lander et al.
Proc. Natl Acad. Sci. USA 1987

Similar Publications