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BIOTEK2021-Bioteknologi for verdiskaping

KSP: Cataloging and utilizing structural variants in DNA to improve sustainability of Norwegian livestock production

Alternative title: Beskrivelse og anvendelse av strukturelle varianter i DNA for økt bærekraft i norsk husdyrproduksjon (CAUSATIVE)

Awarded: NOK 9.8 mill.

In cattle and pigs, the slow transition from wild to domesticated status has taken centuries. However in recent decades this has accelerated as specialized breeding companies began to provide farmers with sperm from a small number of superior individuals, whose value is reflected in their offspring in the form of growth rates, fertility, and docility etc. These traditional qualities are now being supplemented with subtle traits such as milk composition and disposition to inherited disorders, and companies are finding that analysis of DNA can be used to identify mutations associated with both desired and unwelcome traits, and enable the identification of superior bulls and boars when they are still very young. The most widely adopted analytical approach involves measuring thousands of tiny variations in DNA called single nucleotide polymorphisms: SNPs. The specific SNP fingerprint an animal has can predict its potential genetic value and allow breeding companies to build a catalogue of superior individuals. While SNPs are enormously useful, two significant issues affect their predictive power and accuracy. Firstly, information captured by these tiny variations cannot be used to measure large structural variations (SV?s), which can be extremely impactful on an animal?s biology. Secondly, the tools used to interpret SNPs fingerprints use DNA information from breeds developed in the US or UK, and overlooks characteristics unique to Norwegian breeds, weakening our analytical power. CAUSATIVE seeks to address these limitations by developing representations of the DNA in Norwegian cattle and pig breeds that capture SVs from multiple individuals. This data will improve accuracy and precision when calculating genetic value based on SNPs, allow breeders to incorporate knowledge about SV?s in their evaluations (something that has been completely overlooked before now) and understand more about the way an animal?s DNA code affects its biology and health.

For centuries, farmers bred superior livestock by observing how particular individuals, or their offspring, perform in terms of growth, fertility etc. In recent decades, the challenge of producing superior animals has been addressed by breeding companies by implementing elaborate systems to methodically record production traits. By considering this information within a known pedigree structure, it was possible to ensure that animals with superior potential were maintained and used for breeding. This success is based on the fact that genetic variation explains (to varying degree) trait variation. Over the last 10 years, breeding companies have transitioned towards genetic testing as a strategy to measure individual genetic variation with unprecedented accuracy; so called SNP genotyping. Combined with extensive measurement recordings and classical methodology this has allowed them to significantly improve multiple traits simultaneously, and today thousands of cattle and pigs are genetically tested each year and their genetic value calculated. Unfortunately the entire approach is founded on testing one specific type of genetic variation and disregards the important class structural variants (SVs) present in all genome. Moreover, all analysis is founded on a gold-standard reference genome representing a single individual from non-Norwegian breeds. In CAUSATIVE, scientists at NMBU and from Norwegian breeding companies (Geno and Norsvin) will use state-of-the-art sequencing and bioinformatic tools to build novel reference genomes for Norwegian breeds that capture all structural variations present in the population. Breeding companies will use these resources to improve their ability to calculate breeding values and to find ways to select for SVs that until now have been invisible in SNP genotyping data. Finally, we will use our new understanding of genome architecture to identify SVs associated with increasing sustainable production.

Funding scheme:

BIOTEK2021-Bioteknologi for verdiskaping