Faculty Opinions recommendation of Phylogenetic shadowing of primate sequences to find functional regions of the human genome.

2003 ◽  
Author(s):  
Ulf Pettersson
Keyword(s):  
Human Genome ◽  
Functional Regions

scholarly journals An Upper Limit on the Functional Fraction of the Human Genome

2017 ◽  
Vol 9 (7) ◽  
pp. 1880-1885 ◽  
Author(s):  
Dan Graur
Keyword(s):  
Human Genome ◽  
Human Population ◽  
Mutational Load ◽  
Deleterious Mutations ◽  
Replacement Level ◽  
Functional Regions ◽  
Upper Limit ◽  
Constant Size ◽  
Mean Fitness ◽  
The Mean

AbstractFor the human population to maintain a constant size from generation to generation, an increase in fertility must compensate for the reduction in the mean fitness of the population caused, among others, by deleterious mutations. The required increase in fertility due to this mutational load depends on the number of sites in the genome that are functional, the mutation rate, and the fraction of deleterious mutations among all mutations in functional regions. These dependencies and the fact that there exists a maximum tolerable replacement level fertility can be used to put an upper limit on the fraction of the human genome that can be functional. Mutational load considerations lead to the conclusion that the functional fraction within the human genome cannot exceed 15%.

scholarly journals Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease

2016 ◽  
Author(s):  
Qiongshi Lu ◽  
Ryan L. Powles ◽  
Sarah Abdallah ◽  
Derek Ou ◽  
Qian Wang ◽  
...  
Keyword(s):  
Human Genome ◽  
Functional Annotation ◽  
Late Onset ◽  
Complex Diseases ◽  
Tissue Specific ◽  
Functional Regions ◽  
Genome Wide ◽  
Dna Elements ◽  
Human Complex

AbstractContinuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer’s disease (LOAD). Our analyses suggest a strong connection between LOAD heritability and genetic variants contained in regions of the genome functional in monocytes. Furthermore, we show that LOAD shares a similar localization of SNPs to monocyte-functional regions with Parkinson’s disease. Overall, we demonstrate that integrated genome annotations at the single tissue level provide a valuable tool for understanding the etiology of complex human diseases. Our GenoSkyline-Plus annotations are freely available at http://genocanyon.med.yale.edu/GenoSkyline.Author SummaryAfter years of community efforts, many experimental and computational approaches have been developed and applied for functional annotation of the human genome, yet proper annotation still remains challenging, especially in non-coding regions. As complex disease research rapidly advances, increasing evidence suggests that non-coding regulatory DNA elements may be the primary regions harboring risk variants in human complex diseases. In this paper, we introduce GenoSkyline-Plus, a principled annotation framework to identify tissue and cell type-specific functional regions in the human genome through integration of diverse high-throughput epigenomic and transcriptomic data. Through validation of known non-coding tissue-specific regulatory regions, enrichment analyses on 45 complex traits, and an in-depth case study of neurodegenerative diseases, we demonstrate the ability of GenoSkyline-Plus to accurately identify tissue-specific functionality in the human genome and provide unbiased, genome-wide insights into the genetic basis of human complex diseases.

scholarly journals Comparative annotation of functional regions in the human genome using epigenomic data

2013 ◽  
Vol 41 (8) ◽  
pp. 4423-4432 ◽  
Author(s):  
Kyoung-Jae Won ◽  
Xian Zhang ◽  
Tao Wang ◽  
Bo Ding ◽  
Debasish Raha ◽  
...  
Keyword(s):  
Human Genome ◽  
Functional Regions

Structural features of the Y chromosome

Development ◽  
1987 ◽  
Vol 101 (Supplement) ◽  
pp. 75-75
Author(s):  
E. Southern
Keyword(s):  
Human Chromosome ◽  
Sex Determination ◽  
Human Genome ◽  
Y Chromosome ◽  
Chromosome Segregation ◽  
Developmental Process ◽  
Structural Features ◽  
Functional Regions ◽  
Intense Activity ◽  
Simple Sequence

Sex determination, as a model for the developmental process in mammals, is undoubtedly the principal reason for the intense activity of research on the Y chromosome. As the smallest human chromosome it also offers a simple system for studying those aspects of the human genome that are less well understood than genes and the control of their expression. These include functional regions, such as the kinetochores and telomeres involved in chromosome segregation and integrity. The regions associated with these functions contain the simple-sequence DNAs discovered more than 25 years ago but whose roles are still not understood. The association of simple-sequence DNA with the more broadly defined heterochromatic regions of the genome is nowhere better seen than in the long arm of the Y chromosome. The four papers that follow describe studies of sequences in the Y chromosome in the region of the telomere of the short arm, in the region of the centromere and within the heterochromatin present on the long arm.

scholarly journals A Statistical Framework to Predict Functional Non-Coding Regions in the Human Genome Through Integrated Analysis of Annotation Data

2015 ◽  
Author(s):  
Qiongshi Lu ◽  
Yiming Hu ◽  
Jiehuan Sun ◽  
Yuwei Cheng ◽  
Kei-Hoi Cheung ◽  
...  
Keyword(s):  
Human Genome ◽  
Genome Annotation ◽  
Human Genetics ◽  
Integrated Analysis ◽  
Whole Genome ◽  
Coding Regions ◽  
Functional Regions ◽  
Statistical Framework ◽  
Annotation Data ◽  
High Throughput Experiments

Identifying functional regions in the human genome is a major goal in human genetics. Great efforts have been made to functionally annotate the human genome either through computational predictions, such as genomic conservation, or high-throughput experiments, such as the ENCODE project. These efforts have resulted in a rich collection of functional annotation data of diverse types that need to be jointly analyzed for integrated interpretation and annotation. Here we present GenoCanyon, a whole-genome annotation method that performs unsupervised statistical learning using 22 computational and experimental annotations thereby inferring the functional potential of each position in the human genome. With GenoCanyon, we are able to predict many of the known functional regions. The ability of predicting functional regions as well as its generalizable statistical framework makes GenoCanyon a unique and powerful tool for whole-genome annotation. The GenoCanyon web server is available at http://genocanyon.med.yale.edu

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

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