Comparative Genomics of right whales

北大西洋露脊鲸是世界上最濒危的大型鲸鱼之一，大约有500头。与其他受保护的鲸鱼物种不同，由于人为死亡和非常低的繁殖率，它没有恢复。有证据表明，生殖问题的一部分是雄性和雌性的生育问题，包括在不同阶段失去妊娠，导致雌性产犊较少，产犊间隔较长。它在陆地上的近亲之一是奶牛，而奶牛品种，如Holsteins，由于长期选择高产牛奶，目前正在经历类似的繁殖危机。由于牛基因组测序的结果，已经有许多大规模的单核苷酸多态(SNPs)与生育性状的遗传关联研究，主要是在奶牛身上，但最近在公牛身上。这导致了大量与生育特征有关的候选基因和基因组区域(工业选择的染色体单倍型)和变种的确定。在不同品种中发现的不同单倍型与不同阶段的妊娠丢失有关，这些单倍型发生的频率不同。在牛身上对特征良好的动物进行大规模分析，并通过精液评估、体外受精、胚胎分裂、妊娠丢失和移植来评估生殖失败阶段的能力，使得能够识别在自然群体中无法发现的候选基因和变异(例如STAT 5A、STAT 5B、FGF2、PGR1、DPR、ITGB5、GHR、FSHR、IGF1、NLPR9、LEP、HSPA1、PAPPA2、POU1F1、MAP1B、PPP1、STAT 5AR11、LOC784935、CACNA1H、LOC617302、LOC 521021、CatSper)。我已经收到了与布罗德研究所合作对北大西洋露脊鲸基因组进行排序的资金，并提出了一种北大西洋露脊鲸、南部露脊鲸和牛以及其他哺乳动物物种的比较基因组学方法，以确定导致生殖问题的候选基因的变异。2014年被宣布为露脊鲸国际年，该物种将成为第一个被测序的大型鲸鱼。我的实验室拥有北大西洋露脊鲸DNA和组织库，包括600个个体的1,100多个样本，占当前物种的75%以上，遗传数据库包含35个微卫星座位的基因图谱、线粒体控制区序列以及MHC I和II基因座的基因类型(http://narightwhale.nrdpfc.ca/)。通过新英格兰水族馆和照片识别目录(数字)对该物种进行的长期实地研究，使过去25年来大多数出生的小牛和它们的母亲得以识别。它提供了有关产奶率、产犊间隔时间和未分娩雌性的信息。最近，我们能够利用数据库确定可能的交配地是大南海峡。它还允许分配约150个父权，提供关于有多个父权的男性和没有父权的男性的信息。我将把北大西洋露脊鲸和南部露脊鲸的基因组与奶牛的基因组进行比较，并评估候选生育基因座存在的变异。DNA库中代表的所有个体都将是信息性SNPs的基因型。我将把鲸鱼的基因类型和等位基因与繁殖性能联系起来，以了解繁殖功能障碍的分子基础。这种基因组和候选基因分析将形成该物种的分子基础，因为它涉及气候变化导致的主要海洋和食物分布变化。

The North Atlantic right whale is one of the most endangered large whales in the world, numbering about 500 individuals. Unlike other protected whale species it is not recovering due to a combination of anthropogenic-caused mortalities and a very poor reproductive rate. There is evidence that part of the reproductive problem is fertility issues both in males and females including loss of pregnancies at various stages leading to females with fewer calves and longer inter-calf intervals. One of its closest terrestrial relatives is the cow and dairy cow breeds, like Holsteins, are currently experiencing a comparable crisis in reproduction, due to long-term selection for high milk production. As a result of the sequencing of the bovine genome there have been many large scale genetic association studies of single nucleotide polymorphisms (SNPs) with fertility traits mainly in cows but more recently in bulls. This had led to the identification of a large number of candidate genes and genomic regions (industry selected chromosomal haplotypes) and variants that are associated with fertility traits. The different haplotypes, identified in various breeds, are associated with pregnancy loss at different stages and these occur at different frequencies. The ability in bovines to perform large-scale analyses of well-characterised animals and assess stages of reproductive failure through semen evaluation, in vitro fertilization, embryo splitting, pregnancy loss and transplantation has allowed identification of candidate genes and variants that could not have been uncovered in a natural population (eg STAT 5A, STAT 5B, FGF2, PGR1, DPR, ITGB5, GHR,FSHR, IGF1,NLPR9, LEP, HSPA1, PAPPa2, POU1F1, MAP1B, PPP1, Stat 5AR11, LOC784935, CACNA1H, LOC617302, LOC 521021, CATsper). I have received funding to sequence the North Atlantic right whale genome in collaboration with the Broad Institute and propose a comparative genomics approach of the North Atlantic right whale, the southern right whale and the cow together with other mammalian species to identify variants at candidate loci contributing to the reproductive problems. 2014 has been declared the international year of the right whale and this species will represent the first large whale genome sequenced. My laboratory holds the North Atlantic right whale DNA and tissue bank of over 1100 samples for 600 individuals and this represents over 75% of the current species and the genetic data-base contains genotype profiles at 35 microsatellite loci, the mitochondrial control region sequence and genotypes at MHC I and II loci (http://narightwhale.nrdpfc.ca/ ). The long-term field study of the species coordinated through the New England Aquarium and the photo-identification catalogue (DIGITS) has allowed identification of most calves born and their mothers for the past 25 years. This provides information on calving rates, calving intervals and nulliparous females. Recently we were able to identify the putative mating ground as the Great South Channel using the data-base. It has also allowed the assignment of about 150 paternities, providing information on males with multiple paternities and males with no paternities. I will compare the North Atlantic and southern right whales genomes with that of the cow and assess the variants present at the candidate fertility loci. All individuals represented in the DNA bank will be genotype at informative SNPs. I will correlate genotypes and alleles of whales with respect to reproductive performance to understand the molecular basis for the reproductive dysfunction. This genomic and candidate gene analysis will form the molecular foundation for the species as it deals with major oceanographic and food distribution changes resulting from climate change.