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 Nanoparticle Exposure Can Awaken Dormant Viruses in the Lungs
16.01.2017 | Helmholtz Zentrum München - Deutsches Forschungszentrum für Gesundheit und Umwelt

nachricht Cholera bacteria infect more effectively with a simple twist of shape
13.01.2017 | Princeton University

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

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

Im Focus: Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

Researchers from the University of Hamburg in Germany, in collaboration with colleagues from the University of Aarhus in Denmark, have synthesized a new superconducting material by growing a few layers of an antiferromagnetic transition-metal chalcogenide on a bismuth-based topological insulator, both being non-superconducting materials.

While superconductivity and magnetism are generally believed to be mutually exclusive, surprisingly, in this new material, superconducting correlations...

Im Focus: Studying fundamental particles in materials

Laser-driving of semimetals allows creating novel quasiparticle states within condensed matter systems and switching between different states on ultrafast time scales

Studying properties of fundamental particles in condensed matter systems is a promising approach to quantum field theory. Quasiparticles offer the opportunity...

Im Focus: Designing Architecture with Solar Building Envelopes

Among the general public, solar thermal energy is currently associated with dark blue, rectangular collectors on building roofs. Technologies are needed for aesthetically high quality architecture which offer the architect more room for manoeuvre when it comes to low- and plus-energy buildings. With the “ArKol” project, researchers at Fraunhofer ISE together with partners are currently developing two façade collectors for solar thermal energy generation, which permit a high degree of design flexibility: a strip collector for opaque façade sections and a solar thermal blind for transparent sections. The current state of the two developments will be presented at the BAU 2017 trade fair.

As part of the “ArKol – development of architecturally highly integrated façade collectors with heat pipes” project, Fraunhofer ISE together with its partners...

Im Focus: How to inflate a hardened concrete shell with a weight of 80 t

At TU Wien, an alternative for resource intensive formwork for the construction of concrete domes was developed. It is now used in a test dome for the Austrian Federal Railways Infrastructure (ÖBB Infrastruktur).

Concrete shells are efficient structures, but not very resource efficient. The formwork for the construction of concrete domes alone requires a high amount of...

Im Focus: Bacterial Pac Man molecule snaps at sugar

Many pathogens use certain sugar compounds from their host to help conceal themselves against the immune system. Scientists at the University of Bonn have now, in cooperation with researchers at the University of York in the United Kingdom, analyzed the dynamics of a bacterial molecule that is involved in this process. They demonstrate that the protein grabs onto the sugar molecule with a Pac Man-like chewing motion and holds it until it can be used. Their results could help design therapeutics that could make the protein poorer at grabbing and holding and hence compromise the pathogen in the host. The study has now been published in “Biophysical Journal”.

The cells of the mouth, nose and intestinal mucosa produce large quantities of a chemical called sialic acid. Many bacteria possess a special transport system...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

12V, 48V, high-voltage – trends in E/E automotive architecture

10.01.2017 | Event News

2nd Conference on Non-Textual Information on 10 and 11 May 2017 in Hannover

09.01.2017 | Event News

Nothing will happen without batteries making it happen!

05.01.2017 | Event News

 
Latest News

Water - as the underlying driver of the Earth’s carbon cycle

17.01.2017 | Earth Sciences

Interfacial Superconductivity: Magnetic and superconducting order revealed simultaneously

17.01.2017 | Materials Sciences

Smart homes will “LISTEN” to your voice

17.01.2017 | Architecture and Construction

VideoLinks
B2B-VideoLinks
More VideoLinks >>>