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For two segregating biallelic loci, encode the allele on a random population haplotype by indicator variables $X,Y$. Their covariance is the linkage disequilibrium coefficient $D$. The squared correlation is $r^2=D^2/[p_A(1-p_A)p_B(1-p_B)]$, between zero and one. It measures how well one marker predicts the other and is undefined if either marker is monomorphic.

// Target: biology.bigb

A chromosomal crossover is a reciprocal exchange of segments between nonsister chromatids of homologous chromosomes during meiosis. It can change the haplotypes inherited at selected genetic loci; whether it does so depends on the transmitted chromatid and interval.

A chromosome carries genes and other genetic material. A haplotype records the alleles carried on one chromosome at specified genetic loci.

Complete linkage in a two-locus model means recombination fraction zero: only parental haplotype combinations are transmitted. Multiple genetic markers in a nonrecombining block represent one haplotype segregation observation.

Under an infinite sites mutation model, two variable sites on one unrecombined rooted tree have nested or disjoint derived-allele clades. At most three of the four biallelic haplotypes can then occur. Observation of all four haplotypes proves that the single-tree, single-mutation-per-site model cannot hold: some ancestral genetic recombination is necessary if recurrent mutation is excluded. The test gives no proof of absence of recombination when only three haplotypes occur.

// Target: biology.bigb

Why can two individually fair allele transmissions fail to be independent? Genetic loci on the same chromosome can travel together through meiosis. This tendency is genetic linkage; in an ordinary two-locus model, detectable genetic linkage means a recombination fraction below $1/2$. A genetic marker can therefore help track a neighboring genetic locus through a pedigree. See Clark, Douglas and Choi, Biology 2e: chromosomal theory and genetic linkage.

Take a diploid individual heterozygous at two genetic loci, with phase-known genotype $AB/ab$: one homologous chromosome carries alleles $A,B$, the other $a,b$. The parental haplotypes are $AB,ab$; the recombinant haplotypes are $Ab,aB$. Assume fair Mendelian segregation, equal probabilities within each reciprocal pair of gametes, and no allele-dependent differences in gamete recovery. If the recombination fraction is $r=0.2$, the gamete probabilities are $0.4,0.4,0.1,0.1$ in that order. Each genetic locus still transmits its two alleles equally, but $P(AB)=0.4$ exceeds $P(A)P(B)=0.25$: fairness at each genetic locus does not imply independence between genetic loci.

At $r=0$, only the parental haplotypes occur, each with probability $0.5$: this is complete genetic linkage. At $r=0.5$, all four haplotypes have probability $0.25$, giving independent assortment. A recombination fraction near $0.5$ alone cannot establish whether the genetic loci lie on different chromosomes or far apart on one chromosome.

Genetic linkage concerns joint transmission through meiosis. Linkage disequilibrium concerns haplotype frequencies in a population, while genetic association compares allele or genotype frequencies with a phenotype. These questions require different observations; pedigrees directly reveal co-transmission.

A locus is a position or region of a genome. An allele specifies an inherited state there; a haplotype specifies states at several loci on one chromosome.

A genetic map turns observations of inherited haplotypes into an ordered account of genetic loci along a chromosome. Its distances describe genetic recombination, which makes the map useful for locating a genetic locus relative to known genetic markers. A genetic map measures inheritance separation; separation measured in base pairs describes positions along DNA. Recombination hotspots help explain why equal numbers of base pairs need not give equal genetic map distances. See T. A. Brown, Genomes, 2nd edition (2002), chapter 5: Mapping Genomes.

Write $d$ for the expected value of the number of chromosomal crossovers encountered along one transmitted chromatid between the chosen genetic loci, measured in morgans; $100d$ is the distance in centimorgans. This counts exchanges along that transmitted chromatid, rather than all exchanges in the four-chromatid meiotic bundle. For a short interval with very few multiple exchanges, the recombination fraction satisfies $r\approx d$: about $1\%$ recombinant gametes then corresponds to about one centimorgan.

For a longer interval, hidden even numbers of chromosomal crossovers make that approximation inaccurate. Under the Haldane mapping function, $d=0.2$ morgans gives $r\approx 0.164840$; conversely $r=0.2$ gives $d\approx 0.255413$ morgans, or $25.5413$ centimorgans. Applying the inverse formula to an already specified genetic map distance would confuse a count with a probability.

Genetic map distances add along ordered adjacent intervals because the total exchange count is the sum of its interval counts. For independent random variables describing counts in disjoint intervals of the Haldane mapping function model, the endpoint recombination fraction instead obeysExactly one interval must change parental origin. Thus $r_1=r_2=0.2$ gives $r_{12}=0.32$, although the two genetic map distances add to approximately $0.510826$ morgans. The simple composition formula requires the stated independence; crossover interference can invalidate it.

A genetic marker is an observed inherited genomic state used to track chromosomes, test genetic association, or perform genetic linkage analysis. Genetic marker alleles need not themselves cause the phenotype. Several genetic markers on one nonrecombining region form a single observed haplotype.

Genetic recombination rearranges inherited genetic material into new combinations. In the meiosis example considered here, chromosomal crossover exchanges segments between nonsister chromatids of homologous chromosomes. A transmitted chromatid can consequently contain DNA from both parental homologues. This produces new haplotypes without requiring a new mutation at either scored genetic locus. See Meiosis.

For phase-known genotype $AB/ab$, a single chromosomal crossover between the selected genetic loci can yield $Ab$ and $aB$ on the participating chromatids; the other two chromatids can remain $AB$ and $ab$. Thus an exchange in the four-chromatid bundle does not mean every resulting gamete is recombinant. Only a chromosomal crossover encountered along the transmitted chromatid within the selected interval affects its two-locus score.

Follow parental origin along the transmitted chromatid from the first genetic locus to the second. Each exchange switches that origin. An odd number of such chromosomal crossovers changes the endpoint combination; an even number restores parental phase. Two exchanges can therefore leave the scored haplotype as $AB$ even though an internal segment came from the other parental homologous chromosome. Recombinant status is relative to the chosen genetic loci, not a complete record of exchanges along the chromosome.

This integer parity distinction connects the physical process of genetic recombination to the observed recombination fraction. It also explains why a long genetic map interval can accumulate many exchanges while its endpoint recombination fraction approaches $1/2$ in the Haldane mapping function model.

A genotype records the inherited alleles carried by an individual at one or more genetic loci. At a two-copy diploid genetic locus with alleles $A,a$, the possible unordered genotypes are $AA,Aa,aa$. The first and last are homozygotes; the middle is a heterozygote. The notation records inherited states, without yet asserting their phenotypes. See NHGRI: genotype.

An unordered $Aa$ combines the two parental orders $Aa$ and $aA$. This small bookkeeping point explains the factor two in Hardy-Weinberg proportions and in an $Aa\times Aa$ cross. If parental origin or arrangement across several genetic loci matters, a phase-known genotype retains extra information about the two haplotypes.

Genotyping determines the alleles carried at chosen genetic loci. A diploid genotype call need not identify its two haplotypes; that additionally requires a phase-known genotype or haplotype estimation.

A haplotype block is a chromosomal region with limited historical genetic recombination, strong local linkage disequilibrium and comparatively few common haplotypes. Its definition is operational and population-dependent; it does not mean that recombination never occurs within it.

// Target: biology.bigb