東華大學圖書館 |

語系: 繁體中文

說明(常見問題)

回圖書館首頁

手機版館藏查詢

登入

回首頁

切換: 標籤 | MARC模式 | ISBD

The role of paternal origin and freq...

Glaser, Rivka Leah.

FindBook

Google Book

Amazon

博客來

The role of paternal origin and frequency of mutations in the paternal age effect.

紀錄類型:	書目-電子資源 : Monograph/item
正題名/作者:	The role of paternal origin and frequency of mutations in the paternal age effect./
作者:	Glaser, Rivka Leah.
面頁冊數:	132 p.
附註:	Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4745.
Contained By:	Dissertation Abstracts International64-10B.
標題:	Biology, Genetics. -
電子資源:	http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3107507

The role of paternal origin and frequency of mutations in the paternal age effect.
Glaser, Rivka Leah.

The role of paternal origin and frequency of mutations in the paternal age effect. - 132 p.

Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4745.

Thesis (Ph.D.)--The Johns Hopkins University, 2004.

More than 20 genetic disorders are known to be associated with advanced paternal age, one-third of which are caused by recurrent mutations that are almost exclusively paternal in origin. We first determined the parental origin of mutations in de novo cases of two craniosynostotic disorders previously shown to have strong paternal age effects, Crouzon and Pfeiffer syndromes. Over 25 different mutations in exons IIIa and IIIc of the fibroblast growth factor receptor 2 (FGFR2) gene have been reported in these disorders, making screening for parental origin of mutation difficult. Four polymorphisms (including two identified by us) were used to determine the parental origin of the mutation in 22 affected individuals by either restriction enzyme digest or allele specific oligonucleotide hybridization. Among these 22 cases, 11 different mutations were found, all of which were paternal in origin. In addition, we showed advanced paternal age in fathers of children with these disorders.Subjects--Topical Terms:

1017730
Biology, Genetics.

The role of paternal origin and frequency of mutations in the paternal age effect.
LDR:03172nmm 2200265 4500 001 1864958
005 20041216133906.5
008 130614s2004 eng d
035 $a (UnM)AAI3107507
035 $a AAI3107507
040 $a UnM $c UnM
100 1 $a Glaser, Rivka Leah. $3 1952422
245 1 4 $a The role of paternal origin and frequency of mutations in the paternal age effect.
300 $a 132 p.
500 $a Source: Dissertation Abstracts International, Volume: 64-10, Section: B, page: 4745.
500 $a Adviser: Ethylin Wang Jabs.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2004.
520 $a More than 20 genetic disorders are known to be associated with advanced paternal age, one-third of which are caused by recurrent mutations that are almost exclusively paternal in origin. We first determined the parental origin of mutations in de novo cases of two craniosynostotic disorders previously shown to have strong paternal age effects, Crouzon and Pfeiffer syndromes. Over 25 different mutations in exons IIIa and IIIc of the fibroblast growth factor receptor 2 (FGFR2) gene have been reported in these disorders, making screening for parental origin of mutation difficult. Four polymorphisms (including two identified by us) were used to determine the parental origin of the mutation in 22 affected individuals by either restriction enzyme digest or allele specific oligonucleotide hybridization. Among these 22 cases, 11 different mutations were found, all of which were paternal in origin. In addition, we showed advanced paternal age in fathers of children with these disorders.
520 $a We then addressed the underlying mechanism(s) of the paternal age effect. As the incidence of disorders with strong paternal age effects increases rapidly with paternal age, we proposed that the frequency of mutations in sperm would increase in the same manner. Here we used Apert syndrome as a model because a paternal age effect and the paternal origin of mutations have been shown, and only two recurrent mutations account for 99% of all cases, unlike the mutational heterogeneity observed in Crouzon and Pfeiffer syndromes. We developed allele specific peptide nucleic acid PCR assays to detect these two mutations in sperm from men 20--80 years old and found that the number of sperm with mutations increased in men older than 60 years old in the general population. This increase in mutation frequency could not fully explain the increase in birth frequency of Apert syndrome with age. Interestingly, 4/15 men who had fathered children with Apert syndrome were relatively young and had higher frequencies of mutant sperm, suggesting that these men are mosaic, possibly resulting from mutations early in spermatogenesis. We also analyzed leukocytes for the two mutations and found no increase with age, suggesting different efficiencies of selection and/or DNA repair mechanisms in germ and somatic cells.
590 $a School code: 0098.
650 4 $a Biology, Genetics. $3 1017730
690 $a 0369
710 2 0 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 64-10B.
790 1 0 $a Jabs, Ethylin Wang, $e advisor
790 $a 0098
791 $a Ph.D.
792 $a 2004
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoapp/servlet/advanced?query=3107507