Iafrate, A. J., Feuk, L., Rivera, M. N., Listewnik, M. L., Donahoe, P. K., Qi, Y. et al. Detection of large-scale variation in the human genome. Nat. Genet. 36, 949-951
ABSTRACT We identified 255 loci across the human genome that contain genomic imbalances among unrelated individuals. Twenty-four variants are present in > 10% of the individuals that we examined. Half of these regions overlap with genes, and many coincide with segmental duplications or gaps in the human genome assembly. This previously unappreciated heterogeneity may underlie certain human phenotypic variation and susceptibility to disease and argues for a more dynamic human genome structure.
Full-textDOI: · Available from: Charles Lee, Aug 24, 2015
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- " ) . There is also an inactive pseudogene , AMYP1 , located within the amylase gene cluster . The haplotype structures of this multigene family are complex and incompletely ascertained , but it is known that there is significant vari - ability in the total number of AMY1 genes ( Gumucio et al . 1988 ; Samuelson et al . 1988 ; Groot et al . 1989a ; Lafrate et al . 2004 ; Perry et al . 2007 ; Carpenter et al . 2015 ) , as well as some variability in the copy number of AMY2 genes ( Carpenter et al . 2015 ) . Humans are unusual in that they have high levels of the salivary ␣ - amylase , apparently due mostly to multiple copies of AMY1 genes . Among pri - mates , multiple copy numbers of AMY1 genes have b"
ABSTRACT: We propose that plant foods containing high quantities of starch were essential for the evolution of the human phenotype during the Pleistocene. Although previous studies have highlighted a stone tool-mediated shift from primarily plant-based to primarily meat-based diets as critical in the development of the brain and other human traits, we argue that digestible carbohydrates were also necessary to accommodate the increased metabolic demands of a growing brain. Furthermore, we acknowledge the adaptive role cooking played in improving the digestibility and palatability of key carbohydrates. We provide evidence that cooked starch, a source of preformed glucose, greatly increased energy availability to human tissues with high glucose demands, such as the brain, red blood cells, and the developing fetus. We also highlight the auxiliary role copy number variation in the salivary amylase genes may have played in increasing the importance of starch in human evolution following the origins of cooking. Salivary amylases are largely ineffective on raw crystalline starch, but cooking substantially increases both their energy-yielding potential and glycemia. Although uncertainties remain regarding the antiquity of cooking and the origins of salivary amylase gene copy number variation, the hypothesis we present makes a testable prediction that these events are correlated.The Quarterly Review of Biology 08/2015; 90(3):251-268. DOI:10.1086/682587 · 5.06 Impact Factor
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- "Initially, for different species such as human (Homo sapiens) (Iafrate et al., 2004), rice (Oryza sativa) (Yu et al., 2013), soybean (Glycine max) (McHale et al., 2012), and barley (Hordeum vulgare) (Muñoz-Amatriaín et al., 2013), the majority of SVs were detected by microarray-based comparative genomic hybridization. However , array-based technology can only detect SVs with sequences that are homologous to probes and cannot determine the exact copy number or breakpoint. "
ABSTRACT: Structural variations (SVs) represent a major source of genetic diversity. However, the functional impact and formation mechanisms of SVs in plant genomes remain largely unexplored. Here, we report a nucleotide-resolution SV map of cucumber (Cucumis sativas) that comprises 26,788 SVs based on deep resequencing of 115 diverse accessions. The largest proportion of cucumber SVs was formed through nonhomologous end-joining rearrangements, and the occurrence of SVs is closely associated with regions of high nucleotide diversity. These SVs affect the coding regions of 1676 genes, some of which are associated with cucumber domestication. Based on the map, we discovered a copy number variation (CNV) involving four genes that defines the Female (F) locus and gives rise to gynoecious cucumber plants, which bear only female flowers and set fruit at almost every node. The CNV arose from a recent 30.2-kb duplication at a meiotically unstable region, likely via microhomology-mediated break-induced replication. The SV set provides a snapshot of structural variations in plants and will serve as an important resource for exploring genes underlying key traits and for facilitating practical breeding in cucumber. © 2015 American Society of Plant Biologists. All rights reserved.The Plant Cell 05/2015; 27(6). DOI:10.1105/tpc.114.135848 · 9.58 Impact Factor
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- "Copy number variations (CNVs) and SVs contribute substantially to human genetic variation (Iafrate et al. 2004; Sebat et al. 2004; Tuzun et al. 2005; Korbel et al. 2007), and the phenotypic impact of CNVs may be larger than that of SNVs (Redon et al. 2006; Stranger et al. 2007; Conrad et al. 2010). The impact of novel changes in genome structure is further illustrated by their role in human genetic disease (Stankiewicz and Lupski 2010; Cooper et al. 2011). "
ABSTRACT: Small insertions and deletions (indels) and large structural variations (SVs) are major contributors to human genetic diversity and disease. However, mutation rates and characteristics of de novo indels and SVs in the general population have remained largely unexplored. We report 332 validated de novo structural changes identified in whole genomes of 250 families, including complex indels, retrotransposon insertions and interchromosomal events. These data indicate a mutation rate of 2.94 indels (1-20bp) and 0.16 SVs (>20bp) per generation. De novo structural changes affect on average 4.1kbp of genomic sequence and 29 coding bases per generation, which is 91 and 52 times more nucleotides than de novo substitutions, respectively. This contrasts with the equal genomic footprint of inherited SVs and substitutions. An excess of structural changes originated on paternal haplotypes. Additionally, we observed a non-uniform distribution of de novo SVs across offspring. These results reveal the importance of different mutational mechanisms to changes in human genome structure across generations. Published by Cold Spring Harbor Laboratory Press.Genome Research 04/2015; DOI:10.1101/gr.185041.114 · 13.85 Impact Factor