Horse Genetics Module Two Modified and Complex Inheritance NNiigghhtt OOwwll EEdduuccaattiioonn aanndd EEqquueessttrriiaann Night Owl Education and Equestrian Module Two: modified and complex inheritance Lesson four: Modified Ratios Introduction Partial dominance Co-dominance Lethal alleles Lethal White Overo Epistasis Penetrance and expressivity Summary Reference Lesson five: Genetic Linkage Introduction Linkage and the gene for equine combined immune deficiency disorder Partial Linkage example of partial linkage Sex Linkage Summary References Lesson six: Complex Traits and Polygenic Inheritance Introduction Continuous Traits Describing the variation for a quantitative trait Continuous Traits are Polygenic How can quantitative genetics be useful to horse-breeders? Running Speed in Race Horses Personality traits, and their possible connections with colour and pattern Summary References Module two assignment Night Owl Education and Equestrian Lesson Four: Modified Ratios Introduction Mono- and di-hybrid crosses do not always give the classical 3:1 and 9:3:3:1 Mendelian ratios. In the examples so far only simple gene action was considered: for each gene one of the alleles has always been completely dominant over the other in the heterozygote. In the case of two genes the genes control two different characters and act separately from one another. Often the situation is more complex than in these examples. The different ways genes are expressed in the phenotype can affect genetic hybrid ratios, especially where there’s an interaction between genes. Modified ratios can also occur because the genes being considered are linked on the same chromosome (for a di-hybrid cross) or because they’re on the sex chromosomes (sex linked). These situations of linkage and sex-linkage are considered in lesson five. Remember: the different ways genes are expressed in the phenotype can affect genetic ratios, especially where there’s an interaction between genes Partial dominance In cases of complete dominance the heterozygote has the same phenotype as the dominant homozygote. This relationship between a pair of alleles provides the simplest situation for study. With partial dominance (also called semi-dominance or incomplete dominance) the heterozygote exhibits a phenotype which is intermediate between the homozygous forms. There’s a well known example in horse genetics, that of the cream dilution gene (the C locus). Alleles at the C locus are responsible for the palomino, buckskin, smokey black, cremello, perlino and smokey cream. The two known alleles are designated C+ and CCr. CCr shows partial dominance. It dilutes red pigment to yellow in a single dose and to pale cream in a double dose. Night Owl Education and Equestrian Horses with a chestnut base colour and genotype C+C+ are chestnut, while those of genotype CCrCCr are cremello. Horses of genotype C+CCr are palomino, a colour intermediate between the phenotypes for the homozygous forms. Hence there are three phenotypes, with heterozygous horses having an “in-between” phenotype. Similarly horses with a brown or bay base colour and genotype C+C+ are brown or bay, while those of genotype CCrCCr are perlino. Horses of genotype C+CCr are buckskin, a colour intermediate between the two. Cream dilution can have a very subtle effect on black pigment and horses with a black base colour are diluted to smokey black (C+CCr), which can look almost black or sometimes brown or liver, or to smokey cream (CCrCCr) which can be a very attractive fawn colour. You should notice that while the CCr is semi-dominant the wild-type C+ allele is effectively recessive since it needs to be homozygous for there to be no dilution of the base colour. The 3:1 phenotypic ratio for a monohybrid cross is modified to 1:2:1 ratio. For example a cross between two palominos gives an expected theoretical ratio of 1 chestnut: 2 palomino: 1 cremello. This is the same as the genotypic ratio since the heterozygotes are of a separate phenotype (i.e. heterozygotes are palomino and not cremello, as they would be in the case of complete dominance of the CCr allele). This ratio is important for palomino breeders, especially those wishing to avoid producing cremello foals. Cremello horses were formerly discriminated against by some of the breed societies, including the American Quarter Horse Association (AQHA) who until recently didn’t allow their registration. However it can be seen that breeding together palominos will always result in some cremello foals, which will make up about ¼ of foals produced from such crosses. Night Owl Education and Equestrian Genetic contributions from sire from dam ↓ C+ CCr C+ 25% chance: C+C+ 25% chance: C+ CCr chestnut palomino CCr 25% chance: C+ CCr 25% chance: CCr CCr palomino cremello Remember ● With partial dominance the heterozygote exhibits a phenotype which is intermediate between the homozygous forms. ● the 3:1 phenotypic ratio for a monohybrid cross is modified to 1:2:1 Co-dominance In co-dominance both alleles are expressed in the phenotype and the heterozygote has the characters of both parents. The inheritance patterns for co-dominance are similar to those for partial dominance. The best known examples of co-dominance are those of the blood groups and blood protein types, for example the AB blood group where animals with blood group AB have both A and B type antibodies in their blood. Co-dominant traits are used especially for parentage testing and for research, including for conservation purposes and for finding important genes involved in genetic disorders. They are discussed further in later parts of the course. Night Owl Education and Equestrian There are also loci with alleles made up of non-coding DNA, i.e. DNA that isn’t responsible for any external phenotype characters. Such loci can have lots of different alleles (because they don’t “do” anything mutations aren’t harmful to them and lots of variation can build up without natural selection throwing it away). Some of these loci are useful as genetic markers in molecular genetic studies. They have, for example, been used to find genes for some important horse genetic disorders, such as equine combined immune deficiency disorder (equine CID, discussed elsewhere in relation to linkage). These loci have phenotypes only at the level of a molecular genetics test, but their inheritance is nevertheless co-dominant in as much as both alleles at a locus can be detected. Remember ● In co-dominance both alleles are expressed in the phenotype and the heterozygote has the characters of both parents. ● The inheritance patterns for co-dominance are similar to those for partial dominance. ● Co-dominant traits are useful for parentage testing and for research, including for conservation and for finding genes involved in genetic disorders. Lethal alleles There are a few well known examples of lethal alleles in horses, including the white allele and the overo allele. The roan allele was formerly thought to be lethal but has recently been shown not to be. Lethal alleles result in modified ratios among surviving foals. It can be important for horse breeders to know about lethal alleles, especially those breeding paint, pinto or coloured horses. Two alleles are known for the gene for white coat colour, symbolised WW and W+. Most horses are not white and have genotype W+W+. The WW allele is rare in most breeds of horse, but occurs in Tennessee Walking Horses, American Albinos and Miniatures, and rarely in Arabians, Standardbreds and Thoroughbreds. Horses with the WW allele are dark-eyed horses with white coats. WW is dominant over W+, so that horses of genotype W+WW are white. These horses are not the same as white sabinos or other pintos or paints, nor are they cremellos (which have blue eyes). No horses are known with the genotype WWWW. Breeding between white horses always produces some coloured foals, indicating that the horses are heterozygous. It would seem that embryos or Night Owl Education and Equestrian foetuses homozygous for allele WW die early in gestation and are then either resorbed or miscarried. WW is therefore acting as a recessive lethal allele. We say that the allele WW is dominant visible and recessive lethal. The following diagram shows how the standard 3:1 phenotypic ratio of a monohybrid cross between white horses is modified to a 2:1 ratio typical of recessive lethal genes. Genetic contributions from stallion from mare ↓ WW W+ WW WWWW WWW+ Dies in utero White W+ WWW+ W+W+ White coloured There appears to be another lethal gene that occasionally causes death in new born Arabian horses. The foals are born a dilute colour (“lavender”) and often result from a difficult foaling. They have neurological problems and fail to stand and nurse. Remember: ● Horse breeders should know about lethal alleles, especially those breeding paint, pied or coloured horses. ● Lethal alleles result in modified ratios among surviving foals. ● For recessive lethal genes the standard 3:1 phenotypic ratio of a monohybrid cross is modified to a 2:1 ratio. Night Owl Education and Equestrian Lethal White Overo A second well known lethal gene is that which causes the white pattern in overo horses. There are various different genes that cause white coat patterning in paints or “coloured” or pied horses, and overo is genetically distinct from other patterns such as tobiano and sabino. Unfortunately the term “overo” is sometimes unhelpfully used to describe any horse with white spotting patterns not due to appaloosa. Overos are heterozygous for a gene that is lethal when homozygous. Thus the overo allele (OO) is dominant for colour pattern but has a recessive lethal effect. The allele also shows something called pleiotropy. This means it has more than one effect on the phenotype (i.e. it affects more than one character). Homozygous foals (OOOO) are all-white with blue eyes and die of complications from intestinal tract abnormalities.