Project Grant 20196701529321

WHILE THERE HAVE BEEN SIGNIFICANT ADVANCES IN RESOLVING THE PATTERN AND NATURE OF SINGLE NUCLEOTIDE POLYMORPHISMS (SNPS), SIMILAR REALIZATIONS FOR LARGER, MORE COMPLEX FORMS OF GENETIC VARIATION ARE NOT FULLY ACHIEVED. MANY PAPERS REVEALED THAT GENOMIC STRUCTURAL VARIATIONS OR STRUCTURAL VARIATIONS (SVS) IN SHORT, INCLUDING COPY NUMBER VARIATIONS (CNVS), ARE COMMON AND ASSOCIATED WITH HUMAN HEALTH AND ANIMAL PRODUCTION. HOWEVER, DETECTING SVS FROM EITHER MICROARRAY OR SHORT-READ SEQUENCING OFTEN SUFFERS FROM LOW SENSITIVITY (30-70%) AND UP TO 85% FALSE DISCOVERY. ANOTHER PROBLEM IS THAT MOST SV DISCOVERY METHODS DO NOT INDICATE WHICH HAPLOTYPE (A.K.A. PHASE BLOCK) BACKGROUND A GIVEN SV RESIDES ON. THEREFORE, SEQUENCE-BASED RESOLUTION OF SVS (WITH BOTH BOUNDARY/BREAKPOINT MAPPED AND HAPLOTYPE-PHASED) AND THE DEVELOPMENT OF HIGH THROUGHPUT GENOTYPING PLATFORMS ARE NEEDED TO ASSESS THEIR ASSOCIATION WITH ECONOMIC TRAITS. DESPITE TREMENDOUS PROGRESS IN GENOME SEQUENCING, DE NOVO ASSEMBLING A PHASED (HAPLOTYPE-RESOLVED) GENOME IS STILL EXPENSIVE UNTIL RECENTLY. CATTLE AND OTHER LIVESTOCK, LIKE HUMAN, ARE WITNESSING FAST INCREASING NUMBERS OF DE NOVO ASSEMBLED GENOMES. NEVERTHELESS, HOW TO EFFICIENTLY ANALYZE, STORE AND UTILIZE THIS RICH INFORMATION IS A BIG CHALLENGE. PAN-GENOME WAS DEFINED AS THE NONREDUNDANT COLLECTION OF ALL DNA SEQUENCE PRESENT IN THE ENTIRE POPULATION, INCLUDING A CORE GENOME, SHARED IN ALL INDIVIDUALS, AS WELL AS A VARIABLE GENOME (A.K.A. INDIVIDUAL-SPECIFIC SEQUENCES) PRESENTED ONLY IN A SUBSET OF THEM. IN LINE WITH THE USDA NIFA INITIATIVES, THIS PROPOSAL OUTLINES A PLAN TO UTILIZE THE 10X GENOMICS CHROMIUM LINKED-READ SEQUENCING AND MAPPING TECHNOLOGIES, AS WELL AS THEIR ASSOCIATED PIPELINES TO DE NOVO ASSEMBLE DOZENS OF REPRESENTATIVE AND PHASED CATTLE DIPLOID GENOMES; IT WILL ATTEMPT TO EVALUATE NEW CATTLE DIPLOID GENOMES USING COMPUTATIONAL AND EXPERIMENTAL APPROACHES FROM A PAN-GENOME PERSPECTIVE; IT ALSO AIMS TO MAP AND PHASE STRUCTURAL VARIATION, INCLUDING COPY NUMBER VARIATION, AND FURTHER TEST THEIR ASSOCIATIONS WITH CATTLE PRODUCTION AND HEALTH TRAITS.