scholarly journals A structural variant in the 5’-flanking region of the TWIST2 gene affects melanocyte development in belted cattle

2016 ◽  
Author(s):  
Nivedita Awasthi Mishra ◽  
Cord Drögemüller ◽  
Vidhya Jagannathan ◽  
Rémy Bruggmann ◽  
Julia Beck ◽  
...  
Keyword(s):  
Neural Crest ◽  
Copy Number ◽  
Genetic Variant ◽  
Coat Color ◽  
Sequence Data ◽  
Ectopic Expression ◽  
Copy Number Variant ◽  
Whole Genome Sequence ◽  
Transgenic Zebrafish ◽  
Aberrant Expression

AbstractBelted cattle have a circular belt of unpigmented hair and skin around their midsection. The belt is inherited as a monogenic autosomal dominant trait. We mapped the causative variant to a 54 kb segment on bovine chromosome 3. Whole genome sequence data of 2 belted and 130 control cattle yielded only one private genetic variant in the critical interval in the two belted animals. The belt-associated variant was a copy number variant (CNV) involving the quadruplication of a 6 kb non-coding sequence located approximately 16 kb upstream of the TWIST2 gene. Increased copy numbers at this CNV were strongly associated with the belt phenotype in a cohort of 239 cases and 1303 controls (p = 1.3 x 10-278). We hypothesized that the CNV causes aberrant expression of TWIST2 during neural crest development, which might negatively affect melanoblasts. Functional studies showed that ectopic expression of bovine TWIST2 in neural crest in transgenic zebrafish led to a decrease in melanocyte numbers. Our results thus implicate an unsuspected involvement of TWIST2 in regulating pigmentation and reveal a non-coding CNV underlying a captivating Mendelian character.Author SummaryBelted cattle, a spontaneous coat color mutant, have been recognized at least 600 years ago. The striking pigmentation pattern probably has arisen in medieval cattle of the Alpine region. The belt still segregates in Brown Swiss cattle and it has become a breed-defining character in the Lakenvelder or Dutch Belted cattle. The belted allele has also been introgressed into Galloways to form the Belted Galloways. We report here the causative genetic variant, a non-coding copy number variant (CNV) upstream of the TWIST2 gene. We hypothesize that the CNV leads to ectopic expression of TWIST2 in the neural crest, which negatively affects melanocyte development. Overexpression of bovine TWIST2 in transgenic zebrafish embryos led to a decrease in melanocyte numbers, which provides functional support for our hypothesis.

scholarly journals Pigment Intensity in Dogs is Associated with a Copy Number Variant Upstream of KITLG

Genes ◽  
2020 ◽  
Vol 11 (1) ◽  
pp. 75 ◽  
Author(s):  
Kalie Weich ◽  
Verena Affolter ◽  
Daniel York ◽  
Robert Rebhun ◽  
Robert Grahn ◽  
...  
Keyword(s):  
Copy Number ◽  
Genome Wide Association Study ◽  
Coat Color ◽  
Sequence Data ◽  
Copy Number Variant ◽  
Color Variation ◽  
Domestic Dog ◽  
Whole Genome Sequence ◽  
Hair Color ◽  
A Genome

Dogs exhibit a wide variety of coat color types, and many genes have been identified that control pigment production, appearance, and distribution. Some breeds, such as the Nova Scotia Duck Tolling Retriever (NSDTR), exhibit variation in pheomelanin pigment intensity that is not explained by known genetic variants. A genome-wide association study comparing light red to dark red in the NSDTR identified a significantly associated region on canine chromosome 15 (CFA 15:23 Mb–38 Mb). Coverage analysis of whole genome sequence data from eight dogs identified a 6 kb copy number variant (CNV) 152 kb upstream of KITLG. Genotyping with digital droplet PCR (ddPCR) confirmed a significant association between an increased copy number with the dark-red coat color in NSDTR (p = 6.1 × 10−7). The copy number of the CNV was also significantly associated with coat color variation in both eumelanin and pheomelanin-based Poodles (p = 1.5 × 10−8, 4.0 × 10−9) and across other breeds. Moreover, the copy number correlated with pigment intensity along the hair shaft in both pheomelanin and eumelanin coats. KITLG plays an important role in melanogenesis, and variants upstream of KITLG have been associated with coat color variation in mice as well as hair color in humans consistent with its role in the domestic dog.

scholarly journals Asthma and its relationship to mitochondrial copy number: Results from the Asthma Translational Genomics Collaborative (ATGC) of the Trans-Omics for Precision Medicine (TOPMed) program

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242364
Author(s):  
Maxwell P. Cocco ◽  
Evan White ◽  
Shujie Xiao ◽  
Donglei Hu ◽  
Angel Mak ◽  
...  
Keyword(s):  
Gene Expression ◽  
Precision Medicine ◽  
Copy Number ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Mtdna Copy Number ◽  
Respiratory Complex ◽  
Mitochondrial Copy Number ◽  
Patient Reported ◽  
Asthma Status

Background Mitochondria support critical cellular functions, such as energy production through oxidative phosphorylation, regulation of reactive oxygen species, apoptosis, and calcium homeostasis. Objective Given the heightened level of cellular activity in patients with asthma, we sought to determine whether mitochondrial DNA (mtDNA) copy number measured in peripheral blood differed between individuals with and without asthma. Methods Whole genome sequence data was generated as part of the Trans-Omics for Precision Medicine (TOPMed) Program on participants from the Study of Asthma Phenotypes and Pharmacogenomic Interactions by Race-ethnicity (SAPPHIRE) and the Study of African Americans, Asthma, Genes, & Environment II (SAGE II). We restricted our analysis to individuals who self-identified as African American (3,651 asthma cases and 1,344 controls). Mitochondrial copy number was estimated using the sequencing read depth ratio for the mitochondrial and nuclear genomes. Respiratory complex expression was assessed using RNA-sequencing. Results Average mitochondrial copy number was significantly higher among individuals with asthma when compared with controls (SAPPHIRE: 218.60 vs. 200.47, P<0.001; SAGE II: 235.99 vs. 223.07, P<0.001). Asthma status was significantly associated with mitochondrial copy number after accounting for potential explanatory variables, such as participant age, sex, leukocyte counts, and mitochondrial haplogroup. Despite the consistent relationship between asthma status and mitochondrial copy number, the latter was not associated with time-to-exacerbation or patient-reported asthma control. Mitochondrial respiratory complex gene expression was disproportionately lower in individuals with asthma when compared with individuals without asthma and other protein-encoding genes. Conclusions We observed a robust association between asthma and higher mitochondrial copy number. Asthma having an effect on mitochondria function was also supported by lower respiratory complex gene expression in this group.

scholarly journals Mutations Upstream of the TBX5 and PITX1 Transcription Factor Genes Are Associated with Feathered Legs in the Domestic Chicken

2020 ◽  
Vol 37 (9) ◽  
pp. 2477-2486 ◽  
Author(s):  
Jingyi Li ◽  
MiOk Lee ◽  
Brian W Davis ◽  
Sangeet Lamichhaney ◽  
Ben J Dorshorst ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Sequence Data ◽  
Ectopic Expression ◽  
Base Change ◽  
Whole Genome Sequence ◽  
Chromosome 15 ◽  
Specific Transcription Factor ◽  
Proposed Model ◽  
Transcription Factor Genes ◽  
Causal Variants

Abstract Feathered leg is a trait in domestic chickens that has undergone intense selection by fancy breeders. Previous studies have shown that two major loci controlling feathered leg are located on chromosomes 13 and 15. Here, we present genetic evidence for the identification of candidate causal mutations at these loci. This was accomplished by combining classical linkage mapping using an experimental cross segregating for feathered leg and high-resolution identical-by-descent mapping using whole-genome sequence data from 167 samples of chicken with or without feathered legs. The first predicted causal mutation is a single-base change located 25 kb upstream of the gene for the forelimb-specific transcription factor TBX5 on chromosome 15. The second is a 17.7-kb deletion located ∼200 kb upstream of the gene for the hindlimb-specific transcription factor PITX1 on chromosome 13. These mutations are predicted to activate TBX5 and repress PITX1 expression, respectively. The study reveals a remarkable convergence in the evolution of the feathered-leg phenotype in domestic chickens and domestic pigeons, as this phenotype is caused by noncoding mutations upstream of the same two genes. Furthermore, the PITX1 causal variants are large overlapping deletions, 17.7 kb in chicken and 44 kb in pigeons. The results of the present study are consistent with the previously proposed model for pigeon that feathered leg is caused by reduced PITX1 expression and ectopic expression of TBX5 in hindlimb buds resulting in a shift of limb identity from hindlimb to more forelimb-like identity.

scholarly journals Analysis of copy number variations in Holstein-Friesian cow genomes based on whole-genome sequence data

2017 ◽  
Vol 100 (7) ◽  
pp. 5515-5525 ◽  
Author(s):  
M. Mielczarek ◽  
M. Frąszczak ◽  
R. Giannico ◽  
G. Minozzi ◽  
John L. Williams ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Copy Number ◽  
Sequence Data ◽  
Copy Number Variations ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Genome Sequence Data ◽  
Holstein Friesian

scholarly journals The assembled Banana dihaploid mitochondrial genome is compact with a high number of gene copies

2022 ◽  
Author(s):  
Shruthy Priya Prakash ◽  
Vaidheki Chandrasekar ◽  
Selvi Subramanian ◽  
Rahamatthunnisha Ummar
Keyword(s):  
Mitochondrial Genome ◽  
Genome Sequence ◽  
Copy Number ◽  
Ribosomal Proteins ◽  
Tandem Repeats ◽  
Sequence Data ◽  
Crop Improvement ◽  
Whole Genome Sequence ◽  
Trna Genes ◽  
Mt Genome

Banana being a major food crop all around the world, attracts various research interests in crop improvement. In banana, complete genome sequences of Musa accuminata and Musa balbisiana are available. However, the mitochondrial genome is not sequenced or assembled. Mitochondrial (mt) genes play an important role in flower and seed development and in Cytoplasmic Male Sterility. Unraveling banana mt genome architecture will be a foundation for understanding inheritance of traits and their evolution. In this study, the complete banana mt genome is assembled from the whole genome sequence data of the Musa acuminata subsp. malaccensis DH-Pahang. The mt genome sequence acquired by this approach was 409574 bp and it contains, 54 genes coding for 25 respiratory complex proteins 15 ribosomal proteins, 12 tRNA genes and two ribosomal RNA gene. Except atpB, rps11 and rps19 other genes are in multiple copies. The copy number is 12 in tRNA genes. In addition, nearly 25% tandem repeats are also present in it. These mt proteins are identical to the mt proteins present in the other members of AA genome and share 98% sequence similarity with M. balbisiana. The C to U RNA editing is profoundly higher (87 vs 13%) in transcripts of M. balbisiana (BB) compared to M. accuminata (AA). The banana AA mitochondrial genome is tightly packed with 233 genes, with less rearrangements and just 5.3% chloroplast DNA in it. The maintenance of high copy number of functional mt genes suggest that they have a crucial role in the evolution of banana.

scholarly journals Extensive Gene Amplification as a Mechanism for Piperacillin-Tazobactam Resistance in Escherichia coli

mBio ◽  
2018 ◽  
Vol 9 (2) ◽  
Author(s):  
Lisa M. Schechter ◽  
David P. Creely ◽  
Cherilyn D. Garner ◽  
Dee Shortridge ◽  
Hoan Nguyen ◽  
...  
Keyword(s):  
Escherichia Coli ◽  
Antibiotic Resistance ◽  
Copy Number ◽  
Sequence Data ◽  
Gene Dosage ◽  
Clinical Isolates ◽  
Whole Genome Sequence ◽  
Content Type ◽  
E Coli ◽  
Protein Levels

ABSTRACT Although the TEM-1 β-lactamase (Bla TEM-1 ) hydrolyzes penicillins and narrow-spectrum cephalosporins, organisms expressing this enzyme are typically susceptible to β-lactam/β-lactamase inhibitor combinations such as piperacillin-tazobactam (TZP). However, our previous work led to the discovery of 28 clinical isolates of Escherichia coli resistant to TZP that contained only bla TEM-1 . One of these isolates, E. coli 907355, was investigated further in this study. E. coli 907355 exhibited significantly higher β-lactamase activity and Bla TEM-1 protein levels when grown in the presence of subinhibitory concentrations of TZP. A corresponding TZP-dependent increase in bla TEM-1 copy number was also observed, with as many as 113 copies of the gene detected per cell. These results suggest that TZP treatment promotes an increase in bla TEM-1 gene dosage, allowing Bla TEM-1 to reach high enough levels to overcome inactivation by the available tazobactam in the culture. To better understand the nature of the bla TEM-1 copy number proliferation, whole-genome sequence (WGS) analysis was performed on E. coli 907355 in the absence and presence of TZP. The WGS data revealed that the bla TEM-1 gene is located in a 10-kb genomic resistance module (GRM) that contains multiple resistance genes and mobile genetic elements. The GRM was found to be tandemly repeated at least 5 times within a p1ESCUM/p1ECUMN-like plasmid when bacteria were grown in the presence of TZP. IMPORTANCE Understanding how bacteria acquire resistance to antibiotics is essential for treating infected patients effectively, as well as preventing the spread of resistant organisms. In this study, a clinical isolate of E. coli was identified that dedicated more than 15% of its genome toward tandem amplification of a ~10-kb resistance module, allowing it to escape antibiotic-mediated killing. Our research is significant in that it provides one possible explanation for clinical isolates that exhibit discordant behavior when tested for antibiotic resistance by different phenotypic methods. Our research also shows that GRM amplification is difficult to detect by short-read WGS technologies. Analysis of raw long-read sequence data was required to confirm GRM amplification as a mechanism of antibiotic resistance.

scholarly journals TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data

2014 ◽  
Vol 24 (11) ◽  
pp. 1881-1893 ◽  
Author(s):  
Gavin Ha ◽  
Andrew Roth ◽  
Jaswinder Khattra ◽  
Julie Ho ◽  
Damian Yap ◽  
...  
Keyword(s):  
Genome Sequence ◽  
Copy Number ◽  
Sequence Data ◽  
Whole Genome Sequence ◽  
Cell Populations ◽  
Whole Genome ◽  
Genome Sequence Data ◽  
Clonal Cell

scholarly journals A Comprehensive Workflow for Read Depth-Based Identification of Copy-Number Variation from Whole-Genome Sequence Data

2018 ◽  
Vol 102 (1) ◽  
pp. 142-155 ◽  
Author(s):  
Brett Trost ◽  
Susan Walker ◽  
Zhuozhi Wang ◽  
Bhooma Thiruvahindrapuram ◽  
Jeffrey R. MacDonald ◽  
...  
Keyword(s):  
Copy Number Variation ◽  
Genome Sequence ◽  
Copy Number ◽  
Sequence Data ◽  
Read Depth ◽  
Whole Genome Sequence ◽  
Whole Genome ◽  
Genome Sequence Data ◽  
Number Variation

scholarly journals Detection of copy number variants in African goats using whole genome sequence data

2020 ◽  
Author(s):  
Wilson Nandolo ◽  
Gábor Mészáros ◽  
Maria Wurzinger ◽  
Liveness J. Banda ◽  
Timothy N. Gondwe ◽  
...  
Keyword(s):  
Copy Number ◽  
Genetic Characterization ◽  
Sequence Data ◽  
Copy Number Variants ◽  
Copy Number Variations ◽  
Whole Genome Sequence ◽  
African Countries ◽  
Body Of Knowledge ◽  
Number Variation ◽  
Cellular Components

Abstract Background Copy number variations (CNV) are a significant source of variation in the genome and are therefore essential to the understanding of genetic characterization. The aim of this study was to develop a fine-scaled copy number variation map for African goats. We used sequence data from multiple breeds and from multiple African countries. Results A total of 253,553 CNV (244,876 deletions and 8,677 duplications) were identified, corresponding to an overall average of 1,393 CNV per animal. The mean CNV length was 3.3 kb, with a median of 1.3 kb. There was substantial differentiation between the populations for some CNV, suggestive of the effect of population-specific selective pressures. A total of 6,231 global CNV regions (CNVR) were found across all animals, representing 59.2 Mb (2.4%) of the goat genome. About 1.6% of the CNVR were present in all 34 breeds and 28.7% were present in all 5 geographical areas across Africa, where animals had been sampled. The CNVR had genes that were highly enriched in important biological functions, molecular functions, and cellular components including retrograde endocannabinoid signaling, glutamatergic synapse and circadian entrainment. Conclusions This study presents the first fine CNV map of African goat based on WGS data and adds to the growing body of knowledge on the genetic characterization of goats.

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