Genetic Recessives and Carrier Codes
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1 Genetic Recessives and Carrier Codes Genetic Recessives Explained Definitions: Haplotype is defined as a group of SNPs located close to each other on the chromosome and that are usually inherited together. SNP (Single Polymorphic Nucleotide) is a DNA sequence variation across paired chromosomes. Allele is one of two forms of a gene or group of genes. We have one copy of a gene on each chromosome. How do we test for genetic recessives? A Holstein UK member can send a DNA sample in for an animal and request a genetic recessive test for Brachyspina, CVM, BLAD, red factor and free martin. These genetic recessives can be divided into two groups; those that are directly predicted and those that are indirectly predicted. Direct tests are where a single causative SNP is used. The genetic recessive is therefore either there or not and is an accurate test. Indirect tests are predicted from groups of alleles on the chromosome, and depending upon the lab, different areas may be used and therefore different levels of accuracy attained. It is therefore important to know whether a recessive test is direct or indirect as the level of accuracy will be affected. Examples: 1. CVM is a directly tested genetic recessive. On the chromosome the SNP expressing it is either there or it is not there. WHFF codes it as CVC (tested carrier) or CVF (tested non carrier). 2. Fertility Haplotypes HH2 and HH3 are an indirect test, with prediction based on a group of SNPs. Recently the causative SNP for HH1 has been discovered by USDA and is being used by some laboratories. 3. Polled is an indirect test, but unlike the other indirect tests it is a dominant allele. 4. Brachyspina was originally an indirect test but we now have a direct test. In the Holstein UK herd book we cannot discriminate between the two types of test, they are all marked as BYC or BYF. Nomenclature: The WHFF registration WG are discussing the recommendation in November 2012 of nomenclature that will show whether a 'recessive' has been identified using a direct or indirect test. Once decided it is hoped that ICAR will accept the standard. Standards and guidelines are being discussed at international levels through WHFF and ICAR.
2 C = carrier F = tested free or non-carrier
3 Haplotypes Questions and Answers Haplotypes have been discovered that are impacting on fertility of cattle. In order to avoid the devastation of failed conceptions or early embryonic death, it is important that haplotypes and their negative effects are understood. With haplotypes becoming a hot topic within the cattle farming industry, here are some of the common questions that every farmer will want answers to so that unnecessary cattle are not lost. What are haplotypes? The term haplotype refers to a group of single-nucleotide polymorphism (SNP) markers that are located at nearby positions on the chromosome and are usually inherited together. Haplotypes are passed on from both parents and whether they cause harm or good depend on how these haplotypes are arranged in the offspring. Why do I need to know about them? Modern genomics tools have been used to identify thousands of haplotypes on each chromosome; each has a positive, neutral or negative association with production, conformation, health and fertility. It is important to identify and understand which haplotypes cause a negative effect in order to breed around them to ensure that these effects are not passed on. What are the negative effects of haplotypes? There are three haplotypes which have been discovered that cause undesirable traits that impact on Holstein fertility. They are known as HH1, HH2 and HH3. Animals can either be carriers (C) or tested noncarriers (T). Reasons as to how these haplotypes impact fertility is unknown, however it is thought that inheritance of the same haplotype from each parent results in failed conception or early embryonic death. Using semen from bulls with these haplotypes results in just over 3% lower conception rate. What are the chances of haplotypes being passed on? 1. If both parents are carriers of an undesirable haplotype (HH1C): There is a 25% chance that there will be an affected offspring that would not survive to birth Of the live offspring, one-third will be unaffected non-carriers and two-thirds will be carriers For example: HH1C Cow (carrier = Rr) x HH1C Cow (carrier = Rr)
4 R = Normal haplotype r = HH1 Haplotype (containing the causative mutation) 2. If the dam is unknown, but the grandsire and bull are both unaffected carriers of an undesirable haplotype (HH1C): There is a 12.5% chance that the resulting embryo will not survive to birth 3. If the cow and the bull were carriers of different haplotypes, e.g. if the cow was HH1C and the bull was HH2C, the following resulting offspring could be expected: 25% non-carriers of both (HH1T and HH2T) 25% carriers of one (HH1C) 25% carriers of the other (HH2C) 25% carriers of both (HH1C and HH2C) What can I do to avoid breeding negative haplotypes? - The automatic reaction to try and eliminate every animal with an undesirable haplotype is not necessarily practical. - It is not deemed practical given that many more undesirable haplotypes are likely to be found. - Breeders should not necessarily avoid bulls with these haplotypes nor cull cows, heifers and calves that are carriers - By eliminating those animals, breeders are likely to do more harm than good as it will lead to significant economic losses in other important and desirable traits. - Computer programmes for mating offer a simple and inexpensive solution for avoiding further breeding of undesirable haplotypes. With this in mind, it is highly recommended that these programmes are used. - Holstein UK s BullSelector and WebMate are being enhanced so that in the future our breeders will have an option to exclude bulls and cows which are carriers of these haplotypes. How do I find out if my cattle are carriers? Please contact member services on or susanboughton@holstein-uk.org Further Reading Holstein USA Holstein USA Interpreting and Utilising New Holstein Genetic Information
5 Dr Kent A Weigel Haplotypes Affecting Fertility and their Impact on Dairy Cattle Breeding Programs For the accompanying Journal Article about Haplotypes, please click here
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