scholarly journals A copy number variant is associated with a spectrum of pigmentation patterns in the rock pigeon (Columba livia)

2019 ◽  
Author(s):  
Rebecca Bruders ◽  
Hannah Van Hollebeke ◽  
E.J. Osborne ◽  
Zev Kronenberg ◽  
Mark Yandell ◽  
...  
Keyword(s):  
Copy Number ◽  
Coat Color ◽  
Chromosome Region ◽  
Copy Number Variant ◽  
Columba Livia ◽  
Color Pattern ◽  
Gene Copy ◽  
Z Chromosome ◽  
Phenotypic Evolution ◽  
Color Patterns

ABSTRACTRock pigeons (Columba livia) display an extraordinary array of pigment pattern variation. One such pattern, Almond, is characterized by a variegated patchwork of plumage colors that are distributed in an apparently random manner. Almond is a sex-linked, semi-dominant trait controlled by the classicalStipper(St) locus. Heterozygous males (ZStZ+sex chromosomes) and hemizygous Almond females (ZStW) are favored by breeders for their attractive plumage. In contrast, homozygous Almond males (ZStZSt) develop severe eye defects and lack all plumage pigmentation, suggesting that higher dosage of the mutant allele is deleterious. To determine the molecular basis of Almond, we compared the genomes of Almond pigeons to non-Almond pigeons and identified a candidateStlocus on the Z chromosome. We found a copy number variant (CNV) within the differentiated region that captures complete or partial coding sequences of four genes, including the melanosome maturation geneMlana. We did not find fixed coding changes in genes within the CNV, but all genes are misexpressed in regenerating feather bud collar cells of Almond birds. Notably, six other alleles at theStlocus are associated with depigmentation phenotypes, and all exhibit expansion of the same CNV. Structural variation atStis linked to diversity in plumage pigmentation and gene expression, and thus provides a potential mode of rapid phenotypic evolution in pigeons.AUTHOR SUMMARYThe genetic changes responsible for different animal color patterns are poorly understood, due in part to a paucity of research organisms that are both genetically tractable and phenotypically diverse. Domestic pigeons (Columba livia) have been artificially selected for many traits, including an enormous variety of color patterns that are variable both within and among different breeds of this single species. We investigated the genetic basis of a sex-linked color pattern in pigeons called Almond that is characterized by a sprinkled pattern of plumage pigmentation. Pigeons with one copy of the Almond allele have desirable color pattern; however, male pigeons with two copies of the Almond mutation have severely depleted pigmentation and congenital eye defects. By comparing the genomes of Almond and non-Almond pigeons, we discovered that Almond pigeons have extra copies of a chromosome region that contains a gene that is critical for the formation of pigment granules. We also found that different numbers of copies of this region are associated with varying degrees of pigment reduction. The Almond phenotype in pigeons bears a remarkable resemblance to Merle coat color mutants in dogs, and our new results from pigeons suggest that similar genetic mechanisms underlie these traits in both species. Our work highlights the role of gene copy number variation as a potential driver of rapid phenotypic evolution.

scholarly journals A copy number variant is associated with a spectrum of pigmentation patterns in the rock pigeon (Columba livia)

PLoS Genetics ◽  
2020 ◽  
Vol 16 (5) ◽  
pp. e1008274 ◽  
Author(s):  
Rebecca Bruders ◽  
Hannah Van Hollebeke ◽  
Edward J. Osborne ◽  
Zev Kronenberg ◽  
Emily Maclary ◽  
...  
Keyword(s):  
Copy Number ◽  
Copy Number Variant ◽  
Columba Livia ◽  
Rock Pigeon

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 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.

Functional significance of preserved color patterns of mollusks from the Gosport Sand (Eocene) of Alabama

1988 ◽  
Vol 62 (01) ◽  
pp. 83-87 ◽  
Author(s):  
Patricia H. Kelley ◽  
Charles T. Swann
Keyword(s):  
Functional Morphology ◽  
Functional Significance ◽  
Intraspecific Variability ◽  
Color Pattern ◽  
Color Patterns ◽  
Historical Factors ◽  
Life Mode ◽  
Molluscan Fauna ◽  
Excellent Preservation ◽  
Architectural Constraints

The excellent preservation of the molluscan fauna from the Gosport Sand (Eocene) at Little Stave Creek, Alabama, has made it possible to describe the preserved color patterns of 15 species. In this study the functional significance of these color patterns is tested in the context of the current adaptationist controversy. The pigment of the color pattern is thought to be a result of metabolic waste disposal. Therefore, the presence of the pigment is functional, although the patterns formed by the pigment may or may not have been adaptive. In this investigation the criteria proposed by Seilacher (1972) for testing the functionality of color patterns were applied to the Gosport fauna and the results compared with life mode as interpreted from knowledge of extant relatives and functional morphology. Using Seilacher's criteria of little ontogenetic and intraspecific variability, the color patterns appear to have been functional. However, the functional morphology studies indicate an infaunal life mode which would preclude functional color patterns. Particular color patterns are instead interpreted to be the result of historical factors, such as multiple adaptive peaks or random fixation of alleles, or of architectural constraints including possibly pleiotropy or allometry. The low variability of color patterns, which was noted within species and genera, suggests that color patterns may also serve a useful taxonomic purpose.

scholarly journals Estimating Copy-Number Proportions: The Comeback of Sanger Sequencing

Genes ◽  
2021 ◽  
Vol 12 (2) ◽  
pp. 283
Author(s):  
Eyal Seroussi
Keyword(s):  
Copy Number ◽  
Sanger Sequencing ◽  
Cytosine Methylation ◽  
Direct Sequencing ◽  
Information Source ◽  
Gene Copy Number ◽  
Cost Effective ◽  
Gene Copy ◽  
Base Editing ◽  
Recent Developments

Determination of the relative copy numbers of mixed molecular species in nucleic acid samples is often the objective of biological experiments, including Single-Nucleotide Polymorphism (SNP), indel and gene copy-number characterization, and quantification of CRISPR-Cas9 base editing, cytosine methylation, and RNA editing. Standard dye-terminator chromatograms are a widely accessible, cost-effective information source from which copy-number proportions can be inferred. However, the rate of incorporation of dye terminators is dependent on the dye type, the adjacent sequence string, and the secondary structure of the sequenced strand. These variable rates complicate inferences and have driven scientists to resort to complex and costly quantification methods. Because these complex methods introduce their own biases, researchers are rethinking whether rectifying distortions in sequencing trace files and using direct sequencing for quantification will enable comparable accurate assessment. Indeed, recent developments in software tools (e.g., TIDE, ICE, EditR, BEEP and BEAT) indicate that quantification based on direct Sanger sequencing is gaining in scientific acceptance. This commentary reviews the common obstacles in quantification and the latest insights and developments relevant to estimating copy-number proportions based on direct Sanger sequencing, concluding that bidirectional sequencing and sophisticated base calling are the keys to identifying and avoiding sequence distortions.

scholarly journals Nongenotoxic ABCB1 activator tetraphenylphosphonium can contribute to doxorubicin resistance in MX-1 breast cancer cell line

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Raimonda Kubiliute ◽  
Indre Januskeviciene ◽  
Ruta Urbanaviciute ◽  
Kristina Daniunaite ◽  
Monika Drobniene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cell Line ◽  
Protein Level ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Common Mechanism ◽  
Dna Hypomethylation ◽  
Mesenchymal Transition ◽  
Molecular Features

AbstractHyperactivation of ABC transporter ABCB1 and induction of epithelial–mesenchymal transition (EMT) are the most common mechanism of acquired cancer chemoresistance. This study describes possible mechanisms, that might contribute to upregulation of ABCB1 and synergistically boost the acquisition of doxorubicin (DOX) resistance in breast cancer MX-1 cell line. DOX resistance in MX-1 cell line was induced by a stepwise increase of drug concentration or by pretreatment of cells with an ABCB1 transporter activator tetraphenylphosphonium (TPP+) followed by DOX exposure. Transcriptome analysis of derived cells was performed by human gene expression microarrays and by quantitative PCR. Genetic and epigenetic mechanisms of ABCB1 regulation were evaluated by pyrosequencing and gene copy number variation analysis. Gradual activation of canonical EMT transcription factors with later activation of ABCB1 at the transcript level was observed in DOX-only treated cells, while TPP+ exposure induced considerable activation of ABCB1 at both, mRNA and protein level. The changes in ABCB1 mRNA and protein level were related to the promoter DNA hypomethylation and the increase in gene copy number. ABCB1-active cells were highly resistant to DOX and showed morphological and molecular features of EMT. The study suggests that nongenotoxic ABCB1 inducer can possibly accelerate development of DOX resistance.

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