Evolutionary fate of retroposed gene copies in the human genome

Until 2019, the human genome was available in only one fully-annotated version, which was the result of 18 years of continuous improvement and revision. Despite dramatic improvements in sequencing technology, no other individual human genome was available as an annotated reference until 2019, when the genome of an Ashkenazi individual was released. In this study, we describe the assembly and annotation of a second individual genome, from a Puerto Rican individual whose DNA was collected as part of the Human Pangenome project. The new genome, called PR1, is the first true reference genome created from an individual of African descent. Due to recent improvements in both sequencing and assembly technology, PR1 is more complete and more contiguous than either the human reference genome (GRCh38) or the Ashkenazi genome. Annotation revealed 42,217 genes (of which 20,168 are protein-coding), including 107 additional gene copies that are present in PR1 and missing from GRCh38. 180 genes have fewer copies in PR1 than in GRCh38, 13 map only partially, and 3 genes (1 protein-coding) from GRCh38 are entirely missing from PR1.

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The complete sequence of a human genome

10.1101/2021.05.26.445798 ◽

2021 ◽

Author(s):

Sergey Nurk ◽

Sergey Koren ◽

Arang Rhie ◽

Mikko Rautiainen ◽

Andrey V. Bzikadze ◽

...

Keyword(s):

Human Genome ◽

Complete Sequence ◽

Protein Coding ◽

Functional Studies ◽

Gene Copies ◽

Genome Sequencing Consortium ◽

Initial Release ◽

Human Genome Sequencing ◽

Acrocentric Chromosomes ◽

First Time

In 2001, Celera Genomics and the International Human Genome Sequencing Consortium published their initial drafts of the human genome, which revolutionized the field of genomics. While these drafts and the updates that followed effectively covered the euchromatic fraction of the genome, the heterochromatin and many other complex regions were left unfinished or erroneous. Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release. The new T2T-CHM13 reference includes gapless assemblies for all 22 autosomes plus chromosome X, corrects numerous errors, and introduces nearly 200 million bp of novel sequence containing 2,226 paralogous gene copies, 115 of which are predicted to be protein coding. The newly completed regions include all centromeric satellite arrays and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies for the first time.

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A reference-quality, fully annotated genome from a Puerto Rican individual

Genetics ◽

10.1093/genetics/iyab227 ◽

2021 ◽

Author(s):

Aleksey V Zimin ◽

Alaina Shumate ◽

Ida Shinder ◽

Jakob Heinz ◽

Daniela Puiu ◽

...

Keyword(s):

Puerto Rican ◽

Human Genome ◽

Continuous Improvement ◽

Reference Genome ◽

Sequencing Technology ◽

Individual Genome ◽

Protein Coding ◽

Gene Copies ◽

Reference Quality ◽

Assembly Technology

Abstract Until 2019, the human genome was available in only one fully-annotated version, GRCh38, which was the result of 18 years of continuous improvement and revision. Despite dramatic improvements in sequencing technology, no other genome was available as an annotated reference until 2019, when the genome of an Ashkenazi individual, Ash1, was released. In this study, we describe the assembly and annotation of a second individual genome, from a Puerto Rican individual whose DNA was collected as part of the Human Pangenome project. The new genome, called PR1, is the first true reference genome created from an individual of African descent. Due to recent improvements in both sequencing and assembly technology, and particularly to the use of the recently completed CHM13 human genome as a guide to assembly, PR1 is more complete and more contiguous than either GRCh38 or Ash1. Annotation revealed 37,755 genes (of which 19,999 are protein-coding), including 12 additional gene copies that are present in PR1 and missing from CHM13. 57 genes have fewer copies in PR1 than in CHM13, 9 map only partially, and 3 genes (all non-coding) from CHM13 are entirely missing from PR1.

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DNA methylation in satellite repeats disorders

Essays in Biochemistry ◽

10.1042/ebc20190028 ◽

2019 ◽

Vol 63 (6) ◽

pp. 757-771 ◽

Cited By ~ 4

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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