An updated genetic map of Peromyscus with chromosomal assignment of linkage groups.

Species across the rodent genus Peromyscus have become prominent models for studying diverse mechanistic and evolutionary processes, including chromosome evolution, infectious disease transmission and human health, ecological adaptation, coat color variation, and parental care. Supporting such diverse research programs has been the development of genetic and genomic resources for species within this genus, including genome data, interspecific chromosome homologies, and a recently developed genetic map. Based on interspecific hybrids between the deer mouse (Peromyscus maniculatus bairdii) and the old-field, or beach, mouse (Peromyscus polionotus) and backcross progeny to Peromyscus maniculatus, a linkage map was developed based on 190 genes and 141 microsatellite loci. However, resolution of several linkage groups with respect to chromosome assignment was lacking and four chromosomes (8, 16, 20, and 21) were not clearly delineated with linkage data alone. The recent development of a high-density map for Peromyscus proved ineffective in resolving chromosome linkage for these four chromosomes. Herein we present an updated linkage map for Peromyscus maniculatus, including linkage group-chromosome assignments, using fluorescence in situ hybridization mapping of BACs and whole chromosome paints. We resolve the previously conflicting chromosome assignment of linkage groups to Chromosomes 8, 16, 20, and 21, and confirm the assignment of linkage groups to Chromosomes 18 and 22. This updated linkage map with validated chromosome assignment provides a solid foundation for chromosome nomenclature for this species.

Changes in and Efficacies of Indications for Invasive Prenatal Diagnosis of Cytogenomic Abnormalities: 13 Years of Experience in a Single Center.

BACKGROUND: Because the future application of cell-free fetal DNA screening is expected to dramatically improve the diagnostic yield and reduce unnecessary invasive procedures, it is time to summarize the indications of invasive prenatal diagnosis. This retrospective study was performed to evaluate the changes and efficacies of indications of invasive procedures for detecting cytogenomic abnormalities from 2000 to 2012. MATERIAL AND METHODS: From our regional obstetric unit, 7818 invasive procedures were referred by indications of advance maternal age (AMA), abnormal ultrasound findings (aUS), abnormal maternal serum screening (aMSS), and family history (FH). Chromosome, fluorescence in situ hybridization (FISH), and array comparative genomic hybridization (aCGH) analyses were performed on chorionic villus sampling (CVS) and amniotic fluid (AF) specimens at the Yale Cytogenetics Laboratory. The abnormal findings from single or combined indications were compared to evaluate the diagnostic yield. RESULTS: The annual caseload declined by 57.2% but the diagnostic yield increased from 7.2% to 13.4%. Chromosomal and genomic abnormalities were detected in 752 cases (9.6%, 752/7818) and 12 cases (4%, 12/303), respectively. Significantly decreased AMA referrals and increased aUS and aMSS referrals were noted. The top 3 indications by diagnostic yield were AMA/aUS (51.4% for CVS, 24.2% for AF), aUS (34.7% for CVS, 14.5% for AF), and AMA/aMSS (17.8% for CVS, 9.9% for AF). CONCLUSIONS: Over a period of 13 years, the indication of aMSS and aUS were increasing while AMA was decreasing for prenatal diagnosis of cytogenomic abnormalities, and there was a continuous trend of reduced invasive procedures. Prenatal evaluation using AMA/aUS was the most effective in detecting chromosomal abnormalities, but better indications for genomic abnormalities are needed.

Continuous-Trait Probabilistic Model for Comparing Multi-species Functional Genomic Data.

A large amount of multi-species functional genomic data from high-throughput assays are becoming available to help understand the molecular mechanisms for phenotypic diversity across species. However, continuous-trait probabilistic models, which are key to such comparative analysis, remain under-explored. Here we develop a new model, called phylogenetic hidden Markov Gaussian processes (Phylo-HMGP), to simultaneously infer heterogeneous evolutionary states of functional genomic features in a genome-wide manner. Both simulation studies and real data application demonstrate the effectiveness of Phylo-HMGP. Importantly, we applied Phylo-HMGP to analyze a new cross-species DNA replication timing (RT) dataset from the same cell type in five primate species (human, chimpanzee, orangutan, gibbon, and green monkey). We demonstrate that our Phylo-HMGP model enables discovery of genomic regions with distinct evolutionary patterns of RT. Our method provides a generic framework for comparative analysis of multi-species continuous functional genomic signals to help reveal regions with conserved or lineage-specific regulatory roles.