The aims of this 5-year project are to (1) initiate and complete the sequencing of the Y chromosomes of five species - rhesus macaque, marmoset, rat, bull, and opossum, and (2) complete the sequencing of the chicken W chromosome (currently ~10% sequenced). NHGRI has approved the targeting of these five Y chromosomes and the chicken W chromosome for full-scale sequencing. The new Y chromosomes will be added to our queue of three current sex chromosome sequencing projects, the mouse Y and the chicken Z and W, which are in various stages of completion. Our goal is to complete the sequence and annotation of all 8 chromosomes by the end of the next 5-year funding period. During the last 18 years, genomic studies have revealed that Y chromosomes are biologically richer and medically more important than anyone would have predicted. These genomic studies recently culminated in the finished and annotated sequences of the human and chimpanzee Y chromosomes, which are, to date, the only sex-specific chromosomes to have been sequenced from any species, vertebrate or invertebrate, plant or animal. Knowledge of the human Y chromosome sequence has allowed researchers to identify and characterize recurrent Y deletions, which have emerged as the most common of the known causes of infertility in men. Comparative sequencing in chimpanzee has shed light on the functional importance of genes on the human Y chromosome. We suspect that the sex-specific chromosomes of six of NHGRI's high-priority sequencing targets - rhesus, marmoset, rat, bull, opossum, and chicken - will also prove to be of great biomedical interest. The sequences of the new Y chromosomes will offer insight into the human Y chromosome's role in health and disease and will provide essential infrastructure for elucidating mammalian and human germ cell development and sperm production. The chicken W chromosome will be the first female-specific chromosome to be sequenced from any species. We anticipate that the sequence of the W chromosome will inform our understanding of human biology by offering insights into female fertility, oogenesis, and sex determination.

Public Health Relevance

In recent decades, genomic studies in human, chimpanzee, and mouse have revealed that Y chromosomes are biologically richer and medically more important than anyone would have predicted. The Y chromosome sequences of five new species - rhesus macaque, marmoset, rat, bull, and opossum - will likely prove to be of great biomedical interest as well, offering insights into the human Y chromosome's role in health and disease and providing the essential infrastructure for elucidating mammalian and human germ cell development and sperm production. The chicken W chromosome, as the female counterpart of the mammalian Y, will inform our understanding of human biology by offering insights into female fertility, oogenesis, and sex determination.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG000257-22
Application #
8252215
Study Section
Genomics, Computational Biology and Technology Study Section (GCAT)
Program Officer
Felsenfeld, Adam
Project Start
1991-01-01
Project End
2014-03-31
Budget Start
2012-04-01
Budget End
2013-03-31
Support Year
22
Fiscal Year
2012
Total Cost
$1,124,076
Indirect Cost
$547,627
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

Showing the most recent 10 out of 18 publications