An Sci 361 1st Edition Lecture 8 Outline of Last Lecture I. Fertility Genesa. Booroola Geneb. Other GenesII. Major Sheep Genesa. BMP-15i. Mutationsb. GDF9c. BMPR-IBi. MutationsOutline of Current Lecture I. Infertility vs. fertilitya. Finding Phenotypesi. IVFII. Geneticsa. Female Fertilityb. Male FertilityCurrent LectureAre the genes involved in increased production also involved in decreased fertility?Infertility in cattle:• Significant decline in reproductive performance in high producing dairy cows (65% to ~35% pregnancy rate)• Two main factors are low fertilization rates and high embryonic loss (Moore et al., 2006, Santos et al., 2004)• Embryonic loss occurs between fertilization and cell differentiation (day 8 post insemination)These notes represent a detailed interpretation of the professor’s lecture. GradeBuddy is best used as a supplement to your own notes, not as a substitute.Fertility genetics is a challenge:• Genetics accounts for one third of the decline in pregnancy rate (Shook 2006)• Many QTL reported for fertility traits• Why is it challenging to identify fertility genes?• Low heritability for most fertility traits?• Inaccurate phenotypes collected in the field?• Different phenotypic measures in different studies?How to find the missing phenotypes of fertility? (Khatib’s lab):• Majority of pregnancy loss occurs before embryo implantation• Major causes of infertility: reduced fertilization rates and embryonic loss (Santos et al. 2004)• Pregnancy = fertilization and normal embryo development• Create reliable and accurate phenotypes using in vitro fertilization (IVF)Why IVF?• IVF provides unified environment (increases power)• Simplifies complex traits into “less complex”• Allows molecular manipulations of embryos (can target specific genes and silence them)Genetics of female fertility:Fertilization rate: # zygote / # fertilizationBlastocyst rate: # blastocyst / # zygote>8,000 fertilizations; >5,500 IVF embryosGenetics of female fertility: approaches:• Genome-wide association study (GWAS)– scanning markers across the genomes of many individuals to find genetic variations associated with a particular phenotype– Need: genetics markers (SNPs), population with phenotypes, and statistical analysis• Candidate pathway/gene analysis (Candidate Gene Approach)Genetics of female fertility: GWAS Approach (Selective genotyping):• Oocytes from 505 cows fertilized by semen samples from 12 bulls• Phenotypes: fertilization and blastocyst rates• DNA pools were constructed from top and bottom 20% of the phenotypic distribution• Pools were genotyped for the 50K SNP chipTake genotype of whole population and compare highest and lowest scores (tails)Genetics of male fertility:• Most fertility studies in cattle have focused on the maternal genome• Breeding schemes in cattle are focused on the selection of elite bulls using progeny testing or genomic selection• Moderate to high heritability of some semen traits• It is not obvious whether males and females contribute equally to fertility