This 3-year project focuses on the mouse and chimpanzee Y chromosomes and the chicken Z and W chromosomes, in the context of NHGRI's goals to sequence the genomes of these animals. We propose to (1) complete the mapping/sequencing of the mouse and chimpanzee Y chromosomes (each currently 50% sequenced) (2) complete the mapping/sequencing of the chicken Z chromosome (currently 30% sequenced) and (3) map/sequence 50% of the chicken W (currently 1% sequenced) as part of a 6-year goal to complete this chromosome. During the last 15 years, genomic studies have revealed that the human Y chromosome is biologically richer and medically more important than anyone would have predicted. These genomic studies recently culminated in a finished and annotated sequence of the human Y chromosome. To date, the human Y is the only sex-specific chromosome to have been sequenced from any species, vertebrate or invertebrate, plant or animal. Knowledge of its sequence allowed researchers to identify and characterize recurrent Y deletions, which have emerged as the most common of the known causes of infertility in men. We expect that the sex-specific chromosomes of three of NGHRI's high-priority sequencing targets - mouse (XX female/XY male), chimpanzee (XX/YY), and chicken (ZWfemale/ZZ male) - will also prove to beof great biomedical interest. The mouse and chimpanzee Ys will represent only the second and third Y chromosomes to be sequenced. We anticipate that the sequences of these Y chromosomes will offer new insight into the human Y's roles in health and disease and will provide essential infrastructure for elucidating mammalian and human germ cell development and spermatogenesis. The chicken Z and W chromosomes will be the first sequenced sex chromosomes from a species in which females, not males, bear the sex- specific chromosome. We anticipate that the sequences of the Z and W will inform our understanding of human biology by offering insights into vertebrate germ cell development, oogenesis, and sex determination.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG000257-18
Application #
7391251
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Peterson, Jane
Project Start
1991-01-01
Project End
2009-03-31
Budget Start
2008-04-01
Budget End
2009-03-31
Support Year
18
Fiscal Year
2008
Total Cost
$1,005,391
Indirect Cost
Name
Whitehead Institute for Biomedical Research
Department
Type
DUNS #
120989983
City
Cambridge
State
MA
Country
United States
Zip Code
02142
Bellott, Daniel W; Skaletsky, Helen; Cho, Ting-Jan et al. (2017) Avian W and mammalian Y chromosomes convergently retained dosage-sensitive regulators. Nat Genet 49:387-394
Hughes, Jennifer F; Skaletsky, Helen; Koutseva, Natalia et al. (2015) Sex chromosome-to-autosome transposition events counter Y-chromosome gene loss in mammals. Genome Biol 16:104
Soh, Y Q Shirleen; Alföldi, Jessica; Pyntikova, Tatyana et al. (2014) Sequencing the mouse Y chromosome reveals convergent gene acquisition and amplification on both sex chromosomes. Cell 159:800-13
Peterson, Julie A; Gitter, Maria; Bougie, Daniel W et al. (2014) Low-frequency human platelet antigens as triggers for neonatal alloimmune thrombocytopenia. Transfusion 54:1286-93
Okumura, Leah M; Lesch, Bluma J; Page, David C (2013) The ligand binding domain of GCNF is not required for repression of pluripotency genes in mouse fetal ovarian germ cells. PLoS One 8:e66062
Wang, Haoyi; Hu, Yueh-Chiang; Markoulaki, Styliani et al. (2013) TALEN-mediated editing of the mouse Y chromosome. Nat Biotechnol 31:530-2
Mueller, Jacob L; Skaletsky, Helen; Brown, Laura G et al. (2013) Independent specialization of the human and mouse X chromosomes for the male germ line. Nat Genet 45:1083-7
Lange, Julian; Noordam, Michiel J; van Daalen, Saskia K M et al. (2013) Intrachromosomal homologous recombination between inverted amplicons on opposing Y-chromosome arms. Genomics 102:257-64
Hughes, Jennifer F; Skaletsky, Helen; Brown, Laura G et al. (2012) Strict evolutionary conservation followed rapid gene loss on human and rhesus Y chromosomes. Nature 483:82-6
Hughes, Jennifer F; Skaletsky, Helen; Page, David C (2012) Sequencing of rhesus macaque Y chromosome clarifies origins and evolution of the DAZ (Deleted in AZoospermia) genes. Bioessays 34:1035-44

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