Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Found: Missing sequence of the human Y chromosome

17.01.2005


Sequence may contain genes controlling stature and tumor development



Scientists report on Friday in the journal Genome Research that they have successfully cloned and characterized a previously intractable DNA sequence: a 554-kilobase-pair genomic segment near the centromere of the human Y chromosome. This sequence contains eight putatively active genes that could be implicated in sex-associated height differences and gonadal tumor development.

This pericentromeric gap was one of the few holes remaining in the "finished" sequence of the human genome reported last October by the International Human Genome Sequencing Consortium. This "finished" sequence was the culmination of a 13-year effort to elucidate the order and orientation of 2.85 billion basepairs that comprise the human genome. The high-quality sequence spanned more than 99% of the euchromatic (gene-containing) portion of the genome with an accuracy of 99.999%, but despite this accomplishment, substantial sections of chromosomal sequences were still missing.


The Y chromosome, a sex chromosome that is specific to the human male, has posed a particular challenge to researchers attempting to decode its sequence. It contains an extraordinary abundance of repetitive elements, including transposons and tandem arrays of satellite sequences. This highly repetitive, transcriptionally dormant genomic landscape, termed "heterochromatin," defines approximately two-thirds of the Y chromosome, including a section spanning the centromere. Such repetitive sequences, although not recalcitrant to cloning, are laborious to assemble, requiring meticulous analysis of complex repeated sequences.

In this case, the challenge was undertaken by a team of scientists led by Gudrun Rappold, Ph.D., Professor of Human Genetics at the University of Heidelberg in Germany. Their manuscript describing this work, published online today and in the February print issue of Genome Research (www.genome.org), presents the sequencing and analysis of 554 kilobases of previously uncharacterized sequence from the pericentromeric region of the Y chromosome. This sequence contains a 450-kilobase "euchromatic island" with eight presumably active genes flanked by repetitive satellite sequences.

To ensure that this 554-kilobase sequence was in fact missing from the "finished" human genome sequence and was not a structural polymorphism present only in a subset of males in the human population, members of Rappold’s laboratory – including Stefan Kirsch, Ph.D., lead author on the paper – tested 100 men of different ethnic origin for the presence of this 554-kilobase fragment. Indeed, the sequence was present in all 100 individuals tested, but not in any female controls, confirming that this sequence was a fundamental part of the Y chromosome.

More surprising, however, was Rappold’s finding that this "missing" sequence was not unique to the Y chromosome. Rather, this sequence exhibited between 95-99% homology to sequences on exactly half (11 of 22) of the other chromosomes in the human genome, including the pericentromeric regions of autosomes (non-sex chromosomes) 1, 2, 3, 4, 9, 10, 11, 14, 15, 16, and 22. This remarkable similarity can be attributed to segmental duplications, a phenomenon whereby large portions of the genome are copied during evolution. Segmental duplications, which emerged during the past 30 million years of primate evolution, are significantly enriched in subtelomeric and pericentromeric sequences, and now comprise approximately 5% of the human genome, were considered to be one of the biggest obstacles to finishing the human genome sequence. "The identification of these segmental duplications suggests an underrepresentation of pericentromeric regions of the acrocentric chromosomes in the current human genome sequence," Rappold pointed out.

The current study was designed as part of a long-term effort to characterize the molecular genetic basis for Y-chromosome-linked phenotypes. Rappold and colleagues had previously physically mapped the GCY locus, which is thought to be the genetic determinant of sex-related stature differences in humans and is in close proximity to the Y centromere. In addition, the GBY, or gonadoblastoma locus, which is responsible for development of tumors associated with the undifferentiated gonad, has been genetically mapped to the region. Because the "missing" sequence described in this study contained eight putatively active genes, further functional testing of these genes may reveal insights into the genetic basis for stature and gonadoblastoma.

Maria A. Smit | EurekAlert!
Further information:
http://www.cshl.edu
http://www.genome.org

More articles from Life Sciences:

nachricht One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie

nachricht The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Spider silk key to new bone-fixing composite

University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.

Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.

Im Focus: Writing and deleting magnets with lasers

Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.

Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...

Im Focus: Gamma-ray flashes from plasma filaments

Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.

The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...

Im Focus: Basel researchers succeed in cultivating cartilage from stem cells

Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.

Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...

Im Focus: Like a wedge in a hinge

Researchers lay groundwork to tailor drugs for new targets in cancer therapy

In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

Invitation to the upcoming "Current Topics in Bioinformatics: Big Data in Genomics and Medicine"

13.04.2018 | Event News

Unique scope of UV LED technologies and applications presented in Berlin: ICULTA-2018

12.04.2018 | Event News

IWOLIA: A conference bringing together German Industrie 4.0 and French Industrie du Futur

09.04.2018 | Event News

 
Latest News

Magnetic nano-imaging on a table top

20.04.2018 | Physics and Astronomy

Start of work for the world's largest electric truck

20.04.2018 | Interdisciplinary Research

Atoms may hum a tune from grand cosmic symphony

20.04.2018 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>