Publications by authors named "Toshio F Yoshimatsu"

13 Publications

  • Page 1 of 1

Whole-genome analysis of Nigerian patients with breast cancer reveals ethnic-driven somatic evolution and distinct genomic subtypes.

Nat Commun 2021 11 26;12(1):6946. Epub 2021 Nov 26.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA.

Black women across the African diaspora experience more aggressive breast cancer with higher mortality rates than white women of European ancestry. Although inter-ethnic germline variation is known, differential somatic evolution has not been investigated in detail. Analysis of deep whole genomes of 97 breast cancers, with RNA-seq in a subset, from women in Nigeria in comparison with The Cancer Genome Atlas (n = 76) reveal a higher rate of genomic instability and increased intra-tumoral heterogeneity as well as a unique genomic subtype defined by early clonal GATA3 mutations with a 10.5-year younger age at diagnosis. We also find non-coding mutations in bona fide drivers (ZNF217 and SYPL1) and a previously unreported INDEL signature strongly associated with African ancestry proportion, underscoring the need to expand inclusion of diverse populations in biomedical research. Finally, we demonstrate that characterizing tumors for homologous recombination deficiency has significant clinical relevance in stratifying patients for potentially life-saving therapies.
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http://dx.doi.org/10.1038/s41467-021-27079-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8626467PMC
November 2021

The Pseudogene Negatively Regulates Antitumor Responses through Inhibition of Innate Immune Defense Mechanisms.

Cancer Res 2021 03 20;81(6):1540-1551. Epub 2021 Jan 20.

Department of Medicine, Center for Clinical Cancer Genetics and Global Health, University of Chicago, Chicago, Illinois.

Innate immune defense mechanisms play a pivotal role in antitumor responses. Recent evidence suggests that antiviral innate immunity is regulated not only by exogenous non-self-RNA but also by host-derived pseudogene RNAs. A growing body of evidence also indicates a biological role for pseudogenes as gene expression regulators or immune modulators. Here, we report an important role for , the pseudogene of the tumor-suppressor gene, in regulating innate immune defense mechanisms in breast cancer cells. expresses a long-noncoding RNA (lncRNA) in breast cancer cells through divergent transcription. Expression of lncRNA- is increased in breast tumors compared with normal breast tissues. Depletion of induces an antiviral defense-like program, including the expression of antiviral genes in breast cancer cells. Furthermore, -deficient cancer cells mimic virus-infected cells by stimulating cytokines and inducing cell apoptosis. Accordingly, depletion of increases host innate immune responses and restricts virus replication. In converse, overexpression of reduces cytokine expression in breast cancer cells. Mechanistically, lncRNA- is localized in the nucleus, binds to the NF-κB subunit RelA, and negatively regulates antiviral gene expression. Finally, in a xenograft mouse model of breast cancer, depletion of stimulates cytokine expression and local immunity, and suppresses tumor growth. Our results suggest an important role for in innate immune defense mechanisms and antitumor responses. This mechanism of antiviral immunity regulated by a host-derived pseudogene RNA may guide the development of novel therapies targeting immune responses in breast cancer. SIGNIFICANCE: This study identifies a novel mechanism of innate immunity driven by a host pseudogene RNA that inhibits innate immune defense mechanisms and antitumor responses through regulation of antiviral gene expression.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-1959DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969461PMC
March 2021

Racial disparities in survival outcomes among breast cancer patients by molecular subtypes.

Breast Cancer Res Treat 2021 Feb 27;185(3):841-849. Epub 2020 Oct 27.

Department of Public Health Sciences, University of Chicago, Chicago, IL, USA.

Purpose: Differences in tumor biology, genomic architecture, and health care delivery patterns contribute to the breast cancer mortality gap between White and Black patients in the US. Although this gap has been well documented in previous literature, it remains uncertain how large the actual effect size of race is for different survival outcomes and the four breast cancer subtypes.

Methods: We established a breast cancer patient cohort at the University of Chicago Comprehensive Cancer Center. We chose five major survival outcomes to study: overall survival, recurrence-free survival, breast-cancer-specific survival, time-to-recurrence and post-recurrence survival. Cox proportional hazards models were used to estimate the hazard ratios between Black and White patients, adjusting for selected patient, tumor, and treatment characteristics, and also stratified by the four breast cancer subtypes.

Results: The study included 2795 stage I-III breast cancer patients (54% White and 38% Black). After adjusting for selected patient, tumor and treatment characteristics, Black patients still did worse than White patients in all five survival outcomes. The racial difference was highest within the HR-/HER2+ subgroup, in both overall survival (hazard ratio = 4.00, 95% CI 1.47-10.86) and recurrence-free survival (hazard ratio = 3.00, 95% CI 1.36-6.60), adjusting for age at diagnosis, cancer stage, and comorbidities. There was also a significant racial disparity within the HR+/HER2- group in both overall survival and recurrence-free survival.

Conclusions: Our study confirmed that racial disparity existed between White and Black breast cancer patients in terms of both survival and recurrence, and found that this disparity was largest among HR-/HER2+ and HR+/HER2- patients.
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http://dx.doi.org/10.1007/s10549-020-05984-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7925344PMC
February 2021

Prevalence of Inherited Mutations in Breast Cancer Predisposition Genes among Women in Uganda and Cameroon.

Cancer Epidemiol Biomarkers Prev 2020 02 23;29(2):359-367. Epub 2019 Dec 23.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, Illinois.

Background: Sub-Saharan Africa (SSA) has a high proportion of premenopausal hormone receptor negative breast cancer. Previous studies reported a strikingly high prevalence of germline mutations in and among Nigerian patients with breast cancer. It is unknown if this exists in other SSA countries.

Methods: Breast cancer cases, unselected for age at diagnosis and family history, were recruited from tertiary hospitals in Kampala, Uganda and Yaoundé, Cameroon. Controls were women without breast cancer recruited from the same hospitals and age-matched to cases. A multigene sequencing panel was used to test for germline mutations.

Results: There were 196 cases and 185 controls with a mean age of 46.2 and 46.6 years for cases and controls, respectively. Among cases, 15.8% carried a pathogenic or likely pathogenic mutation in a breast cancer susceptibility gene: 5.6% in , 5.6% in , 1.5% in , 1% in , 0.5% in , 0.5% in , and 0.5% in . Among controls, 1.6% carried a mutation in one of these genes. Cases were 11-fold more likely to carry a mutation compared with controls (OR = 11.34; 95% confidence interval, 3.44-59.06; < 0.001). The mean age of cases with mutations was 38.3 years compared with 46.7 years among other cases without such mutations ( = 0.03).

Conclusions: Our findings replicate the earlier report of a high proportion of mutations in among patients with symptomatic breast cancer in SSA.

Impact: Given the high burden of inherited breast cancer in SSA countries, genetic risk assessment could be integrated into national cancer control plans.
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http://dx.doi.org/10.1158/1055-9965.EPI-19-0506DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7007381PMC
February 2020

Germline variants and somatic mutation signatures of breast cancer across populations of African and European ancestry in the US and Nigeria.

Int J Cancer 2019 12 27;145(12):3321-3333. Epub 2019 Jun 27.

Center for Clinical Cancer Genetics & Global Health, Department of Medicine, University of Chicago, Chicago, IL.

Somatic mutation signatures may represent footprints of genetic and environmental exposures that cause different cancer. Few studies have comprehensively examined their association with germline variants, and none in an indigenous African population. SomaticSignatures was employed to extract mutation signatures based on whole-genome or whole-exome sequencing data from female patients with breast cancer (TCGA, training set, n = 1,011; Nigerian samples, validation set, n = 170), and to estimate contributions of signatures in each sample. Association between somatic signatures and common single nucleotide polymorphisms (SNPs) or rare deleterious variants were examined using linear regression. Nine stable signatures were inferred, and four signatures (APOBEC C>T, APOBEC C>G, aging and homologous recombination deficiency) were highly similar to known COSMIC signatures and explained the majority (60-85%) of signature contributions. There were significant heritable components associated with APOBEC C>T signature (h = 0.575, p = 0.010) and the combined APOBEC signatures (h = 0.432, p = 0.042). In TCGA dataset, seven common SNPs within or near GNB5 were significantly associated with an increased proportion (beta = 0.33, 95% CI = 0.21-0.45) of APOBEC signature contribution at genome-wide significance, while rare germline mutations in MTCL1 was also significantly associated with a higher contribution of this signature (p = 6.1 × 10 ). This is the first study to identify associations between germline variants and mutational patterns in breast cancer across diverse populations and geography. The findings provide evidence to substantiate causal links between germline genetic risk variants and carcinogenesis.
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http://dx.doi.org/10.1002/ijc.32498DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6851589PMC
December 2019

Author Correction: Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

Nat Commun 2019 01 14;10(1):288. Epub 2019 Jan 14.

Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

The original version of this Article contained an error in the author affiliations. The affiliation of Kevin P. White with Tempus Labs, Inc. Chicago, IL, USA was inadvertently omitted. This has now been corrected in both the PDF and HTML versions of the Article.
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http://dx.doi.org/10.1038/s41467-018-07886-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6331546PMC
January 2019

Characterization of Nigerian breast cancer reveals prevalent homologous recombination deficiency and aggressive molecular features.

Nat Commun 2018 10 16;9(1):4181. Epub 2018 Oct 16.

Department of Surgery, Lagos State University Teaching Hospital, Ikeja, Lagos, Nigeria.

Racial/ethnic disparities in breast cancer mortality continue to widen but genomic studies rarely interrogate breast cancer in diverse populations. Through genome, exome, and RNA sequencing, we examined the molecular features of breast cancers using 194 patients from Nigeria and 1037 patients from The Cancer Genome Atlas (TCGA). Relative to Black and White cohorts in TCGA, Nigerian HR + /HER2 - tumors are characterized by increased homologous recombination deficiency signature, pervasive TP53 mutations, and greater structural variation-indicating aggressive biology. GATA3 mutations are also more frequent in Nigerians regardless of subtype. Higher proportions of APOBEC-mediated substitutions strongly associate with PIK3CA and CDH1 mutations, which are underrepresented in Nigerians and Blacks. PLK2, KDM6A, and B2M are also identified as previously unreported significantly mutated genes in breast cancer. This dataset provides novel insights into potential molecular mechanisms underlying outcome disparities and lay a foundation for deployment of precision therapeutics in underserved populations.
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http://dx.doi.org/10.1038/s41467-018-06616-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6191428PMC
October 2018

Intensive Surveillance with Biannual Dynamic Contrast-Enhanced Magnetic Resonance Imaging Downstages Breast Cancer in Mutation Carriers.

Clin Cancer Res 2019 03 28;25(6):1786-1794. Epub 2018 Aug 28.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, Illinois.

Purpose: To establish a cohort of high-risk women undergoing intensive surveillance for breast cancer. We performed dynamic contrast-enhanced MRI every 6 months in conjunction with annual mammography (MG). Eligible participants had a cumulative lifetime breast cancer risk ≥20% and/or tested positive for a pathogenic mutation in a known breast cancer susceptibility gene.

Results: Between 2004 and 2016, we prospectively enrolled 295 women, including 157 mutation carriers (75 , 61 ); participants' mean age at entry was 43.3 years. Seventeen cancers were later diagnosed: 4 ductal carcinoma (DCIS) and 13 early-stage invasive breast cancers. Fifteen cancers occurred in mutation carriers (11 , 3 , 1 ). Median size of the invasive cancers was 0.61 cm. No patients had lymph node metastasis at time of diagnosis, and no interval invasive cancers occurred. The sensitivity of biannual MRI alone was 88.2% and annual MG plus biannual MRI was 94.1%. The cancer detection rate of biannual MRI alone was 0.7% per 100 screening episodes, which is similar to the cancer detection rate of 0.7% per 100 screening episodes for annual MG plus biannual MRI. The number of recalls and biopsies needed to detect one cancer by biannual MRI were 2.8 and 1.7 in carriers, 12.0 and 8.0 in carriers, and 11.7 and 5.0 in non- carriers, respectively.

Conclusions: Biannual MRI performed well for early detection of invasive breast cancer in genomically stratified high-risk women. No benefit was associated with annual MG screening plus biannual MRI screening.See related commentary by Kuhl and Schrading, p. 1693.
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http://dx.doi.org/10.1158/1078-0432.CCR-18-0200DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6395536PMC
March 2019

Inherited Breast Cancer in Nigerian Women.

J Clin Oncol 2018 10 21;36(28):2820-2825. Epub 2018 Aug 21.

Yonglan Zheng, Shengfeng Wang, Dezheng Huo, Toshio F. Yoshimatsu, Jing Zhang, Gabriela E.S. Felix, and Olufunmilayo I. Olopade, The University of Chicago, Chicago, IL; Tom Walsh, Suleyman Gulsuner, Silvia Casadei, Ming K. Lee, and Mary-Claire King, University of Washington, Seattle, WA; Temidayo O. Ogundiran, Adeyinka Ademola, Adeyinka G. Falusi, Abideen O. Oluwasola, Adewumi Adeoye, Abayomi Odetunde, Chinedum P. Babalola, Oladosu A. Ojengbede, Stella Odedina, Imaria Anetor, University of Ibadan; Clement A. Adebamowo, Centre for Bioethics and Research, Ibadan, Oyo, Nigeria, and University of Maryland School of Medicine, Baltimore, MD; and Gabriela E.S. Felix, Fundação Oswaldo Cruz and Universidade Federal da Bahia, Bahia, Brazil.

Purpose: Among Nigerian women, breast cancer is diagnosed at later stages, is more frequently triple-negative disease, and is far more frequently fatal than in Europe or the United States. We evaluated the contribution of an inherited predisposition to breast cancer in this population.

Patients And Methods: Cases were 1,136 women with invasive breast cancer (mean age at diagnosis, 47.5 ± 11.5 years) ascertained in Ibadan, Nigeria. Patients were selected regardless of age at diagnosis, family history, or prior genetic testing. Controls were 997 women without cancer (mean age at interview, 47.0 ± 12.4 years) from the same communities. BROCA panel sequencing was used to identify loss-of-function mutations in known and candidate breast cancer genes.

Results: Of 577 patients with information on tumor stage, 86.1% (497) were diagnosed at stage III (241) or IV (256). Of 290 patients with information on tumor hormone receptor status and human epidermal growth factor receptor 2, 45.9% (133) had triple-negative breast cancer. Among all cases, 14.7% (167 of 1,136) carried a loss-of-function mutation in a breast cancer gene: 7.0% in BRCA1, 4.1% in BRCA2, 1.0% in PALB2, 0.4% in TP53, and 2.1% in any of 10 other genes. Odds ratios were 23.4 (95% CI, 7.4 to 73.9) for BRCA1 and 10.3 (95% CI, 3.7 to 28.5) for BRCA2. Risks were also significantly associated with PALB2 (11 cases, zero controls; P = .002) and TP53 (five cases, zero controls; P = .036). Compared with other patients, BRCA1 mutation carriers were younger ( P < .001) and more likely to have triple-negative breast cancer ( P = .028).

Conclusion: Among Nigerian women, one in eight cases of invasive breast cancer is a result of inherited mutations in BRCA1, BRCA2, PALB2, or TP53, and breast cancer risks associated with these genes are extremely high. Given limited resources, prevention and early detection services should be especially focused on these highest-risk women.
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http://dx.doi.org/10.1200/JCO.2018.78.3977DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6161833PMC
October 2018

Comparison of Breast Cancer Molecular Features and Survival by African and European Ancestry in The Cancer Genome Atlas.

JAMA Oncol 2017 12;3(12):1654-1662

Center for Clinical Cancer Genetics, Department of Medicine, The University of Chicago, Chicago, Illinois

Importance: African Americans have the highest breast cancer mortality rate. Although racial difference in the distribution of intrinsic subtypes of breast cancer is known, it is unclear if there are other inherent genomic differences that contribute to the survival disparities.

Objectives: To investigate racial differences in breast cancer molecular features and survival and to estimate the heritability of breast cancer subtypes.

Design, Setting, And Participants: Among a convenience cohort of patients with invasive breast cancer, breast tumor and matched normal tissue sample data (as of September 18, 2015) were obtained from The Cancer Genome Atlas.

Main Outcomes And Measures: Breast cancer–free interval, tumor molecular features, and genetic variants.

Results: Participants were 930 patients with breast cancer, including 154 black patients of African ancestry (mean [SD] age at diagnosis, 55.66 [13.01] years; 98.1% [n = 151] female) and 776 white patients of European ancestry (mean [SD] age at diagnosis, 59.51 [13.11] years; 99.0% [n = 768] female). Compared with white patients, black patients had a worse breast cancer-free interval (hazard ratio, HR=1.67; 95% CI, 1.02-2.74; P = .043). They had a higher likelihood of basal-like (odds ratio, 3.80; 95% CI, 2.46-5.87; P < .001) and human epidermal growth factor receptor 2 (ERBB2 [formerly HER2])–enriched (odds ratio, 2.22; 95% CI, 1.10-4.47; P = .027) breast cancer subtypes, with the Luminal A subtype as the reference. Blacks had more TP53 mutations and fewer PIK3CA mutations than whites. While most molecular differences were eliminated after adjusting for intrinsic subtype, the study found 16 DNA methylation probes, 4 DNA copy number segments, 1 protein, and 142 genes that were differentially expressed, with the gene-based signature having an excellent capacity for distinguishing breast tumors from black vs white patients (cross-validation C index, 0.878). Using germline genotypes, the heritability of breast cancer subtypes (basal vs nonbasal) was estimated to be 0.436 (P = 1.5 × 10−14). The estrogen receptor–positive polygenic risk score built from 89 known susceptibility variants was higher in blacks than in whites (difference, 0.24; P = 2.3 × 10−5), while the estrogen receptor–negative polygenic risk score was much higher in blacks than in whites (difference, 0.48; P = 2.8 × 10−11).

Conclusions And Relevance: On the molecular level, after adjusting for intrinsic subtype frequency differences, this study found a modest number of genomic differences but a significant clinical survival outcome difference between blacks and whites in The Cancer Genome Atlas data set. Moreover, more than 40% of breast cancer subtype frequency differences could be explained by genetic variants. These data could form the basis for the development of molecular targeted therapies to improve clinical outcomes for the specific subtypes of breast cancers that disproportionately affect black women. Findings also indicate that personalized risk assessment and optimal treatment could reduce deaths from aggressive breast cancers for black women.
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http://dx.doi.org/10.1001/jamaoncol.2017.0595DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5671371PMC
December 2017

Identification of a circulating microRNA signature to distinguish recurrence in breast cancer patients.

Oncotarget 2016 08;7(34):55231-55248

Section of Hematology and Oncology, Department of Medicine, University of Chicago, Chicago, IL, USA.

There is an urgent need for novel noninvasive prognostic biomarkers for monitoring the recurrence of breast cancer. The purpose of this study is to identify circulating microRNAs that can predict breast cancer recurrence. We conducted a microRNA profiling experiment in serum samples from 48 breast cancer patients using Exiqon miRCURY microRNA RT-PCR panels. Significantly differentiated miRNAs for recurrence in the discovery profiling were further validated in an independent set of sera from 20 patients with breast cancer recurrences and 22 patients without recurrences. We identified seven miRNAs that were differentially expressed between breast cancer patients with and without recurrences, including four miRNAs upregulated (miR-21-5p, miR-375, miR-205-5p, and miR-194-5p) and three miRNAs downregulated (miR-382-5p, miR-376c-3p, and miR-411-5p) for recurrent patients. Using penalized logistic regression, we built a 7-miRNA signature for breast cancer recurrence, which had an excellent discriminating capacity (concordance index=0.914). This signature was significantly associated with recurrence after adjusting for known prognostic factors, and it was applicable to both hormone-receptor positive (concordance index=0.890) and triple-negative breast cancers (concordance index=0.942). We also found the 7-miRNA signature were reliably measured across different runs of PCR experiments (intra-class correlation coefficient=0.780) and the signature was significantly higher in breast cancer patients with recurrence than healthy controls (p=1.1x10-5). In conclusion, circulating miRNAs are promising biomarkers and the signature may be developed into a minimally invasive multi-marker blood test for continuously monitoring the recurrence of breast cancer. It should be further validated for different subtypes of breast cancers in longitudinal studies.
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http://dx.doi.org/10.18632/oncotarget.10485DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5342414PMC
August 2016

Microsatellites in the estrogen receptor (ESR1, ESR2) and androgen receptor (AR) genes and breast cancer risk in African American and Nigerian women.

PLoS One 2012 11;7(7):e40494. Epub 2012 Jul 11.

Center for Clinical Cancer Genetics and Global Health, Department of Medicine, The University of Chicago, Chicago, Illinois, United States of America.

Genetic variants in hormone receptor genes may be crucial predisposing factors for breast cancer, and microsatellites in the estrogen receptor (ESR1, ESR2) and androgen receptor (AR) genes have been suggested to play a role. We studied 258 African-American (AA) women with breast cancer and 259 hospital-based controls, as well as 349 Nigerian (NG) female breast cancer patients and 296 community controls. Three microsatellites, ESR1_TA, ESR2_CA and AR_CAG, in the ESR1, ESR2 and AR genes, respectively, were genotyped. Their repeat lengths were then analyzed as continuous and dichotomous variables. Analyses of continuous variables showed no association with breast cancer risk in either AA or NG at ESR1_TA; AA cases had shorter repeats in the long allele of ESR2_CA than AA controls (Mann-Whitney P= 0.036; logistic regression P = 0.04, OR= 0.91, 95% CI 0.83-1.00), whereas NG patients had longer repeats in the short allele than NG controls (Mann-Whitney P= 0.0018; logistic regression P= 0.04, OR= 1.06, 95% CI 1.00-1.11); and AA cases carried longer repeats in the short allele of AR_CAG than AA controls (Mann-Whitney P= 0.038; logistic regression P = 0.03, OR= 1.08, 95% CI 1.01-1.15). When allele sizes were categorized as dichotomous variables, we discovered that women with two long alleles of ESR2_CA had increased risk of breast cancer (OR = 1.38, 95% CI 1.10-1.74; P = 0.006). This is the first study to investigate these three microsatellites in hormonal receptor genes in relation to breast cancer risk in an indigenous African population. After adjusting for multiple-testing, our findings suggest that ESR2_CA is associated with breast cancer risk in Nigerian women, whereas ESR1_TA and AR_CAG seem to have no association with the disease among African American or Nigerian women.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0040494PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3394707PMC
January 2013

Retrogene movement within- and between-chromosomes in the evolution of Drosophila genomes.

Gene 2006 Dec 23;385:96-102. Epub 2006 Sep 23.

Committee on Genetics, The University of Chicago, 1101 E 57th Street, Chicago, IL 60637, USA.

Recent genomic analyses in Drosophila and mammals of inter-chromosomal retroposition have revealed that during evolution the retroposed genes that show male-biased expression tend to leave the X chromosome and opt for autosomal positions. Such a phenomenon may be a process of general, genomic and evolutionary relevance. It contributed to the unexpected overrepresentation of male-biased genes on the autosomes recently observed in microarray expression experiments. In this paper, we report our genomic analysis of within-chromosomal retroposition in Drosophila melanogaster, and compare it with the previously identified pattern of the between-chromosomal retroposition. We find that a surfeit of autosomal retroposed genes originated from parental genes located on the same chromosome, in contrast to the X chromosome in which only few genes retroposed in cis. Such an autosomal proximity effect implicates a role of the mutation process for retroposition in determining chromosomal locations of autosome-derived retroposed genes. Furthermore, this phenomenon supports the hypothesis that natural selection favors the retroposition of genes out of the X chromosome. Analyses of a large expression database for D. melanogaster genes revealed that the vast majority of the X-derived autosomal retroposed genes had evolved testis expression functions, consistent with other previous genomic analyses.
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http://dx.doi.org/10.1016/j.gene.2006.04.033DOI Listing
December 2006
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