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Identification and analysis of pseud...

Lu, Yongtao.

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Identification and analysis of pseudogenes in the human and mouse genomes.

紀錄類型:	書目-語言資料,印刷品 : Monograph/item
正題名/作者:	Identification and analysis of pseudogenes in the human and mouse genomes./
作者:	Lu, Yongtao.
面頁冊數:	227 p.
附註:	Adviser: David Haussler.
Contained By:	Dissertation Abstracts International68-05B.
標題:	Biology, Bioinformatics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3265723
ISBN:	9780549042372

Identification and analysis of pseudogenes in the human and mouse genomes.
Lu, Yongtao.

Identification and analysis of pseudogenes in the human and mouse genomes. - 227 p.

Adviser: David Haussler.

Thesis (Ph.D.)--University of California, Santa Cruz, 2007.

Pseudogenes are relatives of genes that lose the ability to produce functional products. Pseudogenes comprise a significant portion of vertebrate genomes and are especially prevalent in mammalian genomes. Pseudogene identification is an important problem in computational genomics, and is critical for the identification and characterization of functional elements in the genome. Without separating genes and pseudogenes, it is impossible to obtain an accurate picture of a genome's structure and function.

ISBN: 9780549042372Subjects--Topical Terms:

1018415
Biology, Bioinformatics.

Identification and analysis of pseudogenes in the human and mouse genomes.
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245 1 0 $a Identification and analysis of pseudogenes in the human and mouse genomes.
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520 $a Pseudogenes are relatives of genes that lose the ability to produce functional products. Pseudogenes comprise a significant portion of vertebrate genomes and are especially prevalent in mammalian genomes. Pseudogene identification is an important problem in computational genomics, and is critical for the identification and characterization of functional elements in the genome. Without separating genes and pseudogenes, it is impossible to obtain an accurate picture of a genome's structure and function.
520 $a We have developed a homology-based computational pseudogene finding pipeline - PseudoFinder. PseudoFinder can comprehensively and consistently search and identify pseudogenes in a mammalian genome. Unlike many other pseudogene finding methods that identify pseudogenes based on a set of preset rules, PseudoFinder takes a machine learning approach. It first learns rules that distinguish pseudogenes from genes in a set of training samples and then applies these rules to identify pseudogenes. Our results show that PseudoFinder performs as well as other pseudogene finding methods and even better in some aspects.
520 $a We identified pseudogenes in the most recently assembled human and mouse genome sequences using PseudoFinder, and analyzed human and mouse pseudogenes. Because the mechanism of pseudogene biogenesis is the same in human and mouse, human and mouse pseu dogenes share many similar aspects, such as similar composition of different types of pseudogenes. Both human and mouse show an unusual high pseudogene density on sex chromosomes compared to autosomal chromosomes because of the unique biogenesis history of sex chromosomes. However, each species has its own unique active pseudogene producing genes that leave hundreds pseudogenes in its genome. The two types of pseudogenes, processed and nonprocessed pseudogenes, have quite different characteristics because the biogenesis mechanisms are different between them. Compared to genes, pseudogenes have a much higher Ka/Ks ratio, while the sequence divergence between pseudogenes and their parental genes is lower than that between homologous genes. Our study also shows that some pseudogenes are transcribed, and each species has a set of genes inactivated during evolution.
520 $a We discovered the human gp25L pseudogene, a gene that was disabled by a nonsense mutation only in the human species. The gp25L gene belongs to the p24 gene family, which is involved in the early protein distribution pathway. The p24 gene family is a stable gene family and is present in most eukaryotes, including fungi, plants, worms, fishes, and placental mammals. The origin of the gp25L gene can be at least traced back to before the separation of tunicates and chordates, and it is widely present in chordate species (except human). Our study also showed gp25L has another minor allele containing a destructive defect because of a missense mutation. But both the major and minor alleles are no longer transcribed. All of our data suggests that gp25L has been disabled by positive selection and is completely disabled in the human population by two independent substitution events. Thus, the gp25L gene may have been important in human evolution and will be an interesting object for further study.
520 $a Finally, as part of the ENCyclopedia Of DNA Elements (ENCODE) project, a thorough pseudogene study was carried out on 1% of the human genome sequence. Several distinct pseudogene annotation strategies were applied to the ENCODE regions and from them a consensus approach was applied, identifying 201 pseudogenes, two-thirds of which originated from retrotransposition. 80% of the processed pseudogenes are primate specific sequences, highlighting the increasing retrotransposition activity in primates. In order to explore the functional implication of pseudogene prevalence, the ENCODE consortium performed a systematic series of pseudogene-specific RACE analyses together with complementary evidence derived from tiling microarrays and high-throughput sequencing. Results show that a fifth of the 201 pseudogenes are transcribed in one or more cell lines or tissues.
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