Statistical Approaches

In experimental organisms, genetic mapping of loci involves counting the number of recombinant and nonrecombinant offspring of selected matings. Genetic mapping in humans is usually more complicated than in experimental organisms for many reasons, including researchers' inability to design specific matings of individuals, which limits the unequivocal assignment of recombinants and nonrecombinants. Therefore, maps of markers in humans are developed by means of one of several statistical algorithms used in computer programs.

Genetic maps can assume equal recombination between males and females, or they can allow for sex-specific differences in recombination, since it has been well established that there are substantial differences in recombination frequencies between men and women. Chromosomes recombine more often in females. On average, the female map is two times as long as the male map.

The complexity of the underlying statistical methods used to generate them renders genetic maps sensitive to marker genotyping errors, particularly in small intervals, and these maps are less useful in regions of less than about 2 centimorgans. While marker order is usually correct, genotyping errors can result in falsely inflated estimates of map distances.

Disease gene mapping is greatly facilitated by the availability of dense genetic maps. Linkage analysis for the mapping of disease genes boils down to the simple idea of counting recombinants and nonrecombinants, but in humans this process is complicated for a variety of reasons. The generation time is long in humans, so large, multigenerational pedigrees in which a disease or trait is segregating are rare. Scientists cannot dictate matings or exposures. They also cannot require that specific individuals participate in a study. Thus the process of linkage analysis in humans requires a statistical framework in which various hypotheses about the linkage of a trait locus and marker locus can be considered.

kilobases units of measure of the length of a nucleicacid chain; one kilobase is equal to 1,000 base pairs il pedigrees sets of related individuals, or the graphic representation of their relationships hypotheses testable statements oooc ,oc

How far apart are the disease and marker, and how certain is the conclusion of linkage?

When the inheritance pattern for a disease is clearly known (e.g., autosomal dominant, sex-linked, etc.), the genetic data can be treated with a statistical approach that determines the likelihood that the gene is linked to a particular marker, at a particular position on a specific chromosome. This approach is often termed the "lod score approach," where "lod" is short for logarithm of the odds.

Lod score linkage analysis is used most frequently to consider diseases that follow a Mendelian pattern of transmission within families. Positive lod scores, especially those greater then 3.0, suggest evidence for linkage between a disease gene and a marker locus. Negative lod scores suggest that the disease gene and marker locus are unlinked to one another. see also Crossing Over; Gene Discovery; Human Disease Genes, Identification of; Mapping; Meiosis; Morgan, Thomas Hunt; Polymorphisms.

Marcy C. Speer

Bibliography

Strachan, Tom, and Andrew P. Read. Human Molecular Genetics. New York: Wiley-Liss Publishers, 1999.

Wn Maize

Maize (Zea mays L.), otherwise known as corn, is a highly unusual, economically important, and genetically well-characterized member of the grass family. It is believed to have originated some 8,000 to 10,000 years ago in the fields of the first agriculturalists of Mexico and Central America. These early farmers carefully selected traits that would ultimately transform the tiny, sparsely seeded spike of a wild grass into the large cob bearing many rows of kernels that we recognize today as an ear of corn.

The success of these early plant breeders was manifested by the spread of corn cultivation throughout the New World, long before the arrival of Europeans. Today, maize is grown in more countries than any other crop, and is a major source of food for both humans and domesticated animals throughout the world. The world production of maize in 2000 exceeded 23 billion bushels, the largest producer being the United States (43 percent).

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