Mapping of genes that influence milk production in cattle

Janne Karin Brodin

Understanding what genes influence a trait and the interaction between them will yield important information on how the genome works and will also be an important breeding tool. Results show that a small area on chromosome 6 contains one or more genes that greatly influence the percentage of fat and protein in milk, and we are close to identifying this gene.

Mapping of genes that influence important production and health traits has developed into a major field of research within medicine as well as within farm animal production. Through identifying and characterising these genes and the mutations that create the genetic variation, we gain important insight into the way the genome is made and how it works. We also gather information on how the various genes are influenced by other genes and by the environment.

This knowledge can be a useful supplement to the traditional phenotype based breeding systems, since many of these traits are influenced by an unknown number of genes as well as by the environment. They therefore have a quantitative distribution of phenotype and often also low heritability, and rather complex statistical methods are necessary in order to split an individual’s phenotype into its genetic and environmental components. By identifying the genes (called quantitative trait loci or QTL), we can develop simple gene tests and select breeding animals with the sought-for combinations of genes directly from these.

In our work we wanted to map genes that are important to milk production in Norwegian Red Cattle. We looked at five different characteristics; kg milk, kg protein, kg fat, protein percentage and fat percentage. The mapping itself is done through a series of statistical analyses where the gene or genes can be identified with an increasing degree of accuracy. The first step is a so-called genome scan, in which one finds which chromosomes seem to have genes that are relevant for the trait.

In short, the analysis is about genotyping a family material, in our case six elite bulls with in all 285 proven sons, for a series of genetic markers (short DNA segments with known placement and sequence) spread out over the entire genome. For those markers where the father has two different variants (alleles) of a marker, the sons are split into two groups depending on which allele they have inherited from “dad”. Then, one tests whether one of the groups has a larger heritability breeding value for the trait than the other one, which would indicate that the marker is situated close to a QTL that influences the trait. This analysis pointed to a QTL about midways on chromosome 6 which influenced the percentage of protein and fat in the milk greatly, and had a small and opposite effect on kg milk.

The problem with genome scans is that the method is too unspecific to be able to identify the sought-for gene; there may in fact be thousands of genes in this area. Therefore, the next step is fine mapping. To do this, the animal material must be larger, the set of markers in the relevant interval must be larger, and the methods must be more complex. Through increasing the number of animals to 20 families with in all 1100 sons and genotyping these for 37 markers, we finally managed to narrow down the area where the gene or genes had to be situated to ca. 420 kilobase pairs. This is very precise compared to what normally is achieved in similar studies.

It was not known which genes occupied this area of the bovine genome, but by comparing it with the human genome we found that this area contained six genes. None of these are known to take part in milk production, but one of them has an effect that may be of importance. This gene, polycystic kidney disease 2 (PKD2), is known to cause the corresponding illness in humans. The gene encodes for a membrane protein which is involved in, among other things, calcium transport. It is possible that this gene through influencing the calcium concentration, has an effect on the amount of water in the milk, which indirectly leads to a change in the percentage of fat and protein in the milk. We are now hard at work examining this gene as well as five others more closely, in order to determine which of them it is that influences milk production, and how it works.

Updated: 27.04.11
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