Generation of a Polymorphic Marker Linked to Thymoma Susceptibility Gene of Rat 1 by Genetically-Directed Representational Difference Analysis.

Abstract

BUF/Mna (BUF) is a rat strain susceptible to spontaneous development of thymomas. We have previously shown that the thymoma susceptibility is controlled principally by a dominant susceptibility gene located on chromosome 7, thymoma susceptibility gene of rat 1 (Tsr1). To generate genetic markers tightly linked to Tsr1, we performed genetically directed representational difference analysis (GDRDA) with three combinations of the tester and driver DNAs. From 124 {ACI/NMs × (BUF × ACI/NMs) F 1 } backcross rats, 12 rats with the ACI/BUF genotype in the Tsr1 region (A/B rats) and 13 rats with the ACI/ACI genotype in the region (A/A rats) were selected, and their DNAs were pooled, respectively. Three kinds of tester DNAs, i) inbred BUF, ii) (BUF × ACI)F 1 , and iii) the pool from the A/B rats, were subtracted by the driver DNA prepared from the pool of the A/A rats. The three combinations yielded one, two, and one polymorphic marker(s), respectively. One marker, D7Ncc28, was isolated commonly by the three combinations of subtraction, and another marker, D11Ncc12 was isolated only by the second combination. Linkage analysis demonstrated that D7Ncc28 was located in the 8.3 cM region where Tsr1 has been mapped. The three combinations of subtraction were shown to be almost equally capable of isolating polymorphic markers in a specific chromosomal region.

Affinity Capture and Identification of Host Cell Factors Associated with Hepatitis C Virus (+) Strand Subgenomic RNA

“…ELAC2 has been shown to be associated with prostate cancer as mutation in the gene increases the risk of prostate cancer (69). Another oncogenic protein, KIAA1401, is also a transcriptional system regulator 1 (TSR1) and is required during maturation of the 40 S ribosomal subunit in the nucleolus; it also is associated with breast and thymus cancer (70). Endoplasmic reticulum lipid raft-associated 2 isoform 1 (ERLIN2) has been identified as one of the most potently transforming oncogenes expressed in breast cancer (71).…”

The Bh (Black at Hatch) Gene that Causes Abnormal Feather Pigmentation Maps to Chromosome 1 of the Japanese Quail

“…In GDRDA, a polymerase chain reaction (PCR)‐amplified fragment prepared from a DNA pool of animals having the A / A or A / B genotype for a specific locus (tester amplicon) is subtracted from that of the B / B genotype (driver amplicon). This type of subtraction is known to result in isolation of RFLP markers linked to the specific locus (7–9). We also successfully adapted GDRDA in the Bh mutation and isolated one genetic marker linked to the Bh locus (10).…”

Establishment of thymoma-prone congenic rat strain, ACI.BUF/Mna-Tsr1/Tsr1

“…Dominant trait of the Tsr1 region was also conWrmed in this study. Thus, this congenic strain of rat will be useful for elucidation of the mechanism of the development of thymoma, analyzing the abnormality of genes which locate within the region of the Tsr1, which was deWned by the previous linkage studies (Oyabu et al 1999;Higo et al 2000). It is noteworthy that many genetic aberrations, including losses of heterozygosity and ampliWcations, were found in loci of Chr.…”

“…7 (Oyabu et al 1999). The Tsr1 region narrowed down into the region between D7Wox16 and D7Rat21 (Higo et al 2000). Therefore, we attempted to establish a congenic thymoma-prone strain of rat by placement of the Tsr1 region into the genome of the ACI/NMna strain.…”