Amarilis Sanchez-Valle

Bio: Amarilis Sanchez-Valle is an academic researcher from University of South Florida. The author has contributed to research in topics: Medicine & Offspring. The author has an hindex of 10, co-authored 23 publications receiving 435 citations. Previous affiliations of Amarilis Sanchez-Valle include Baylor College of Medicine.

Identification of uncommon recurrent Potocki-Lupski syndrome-associated duplications and the distribution of rearrangement types and mechanisms in PTLS.

Abstract: Nonallelic homologous recombination (NAHR) can mediate recurrent rearrangements in the human genome and cause genomic disorders. Smith-Magenis syndrome (SMS) and Potocki-Lupski syndrome (PTLS) are genomic disorders associated with a 3.7 Mb deletion and its reciprocal duplication in 17p11.2, respectively. In addition to these common recurrent rearrangements, an uncommon recurrent 5 Mb SMS-associated deletion has been identified. However, its reciprocal duplication predicted by the NAHR mechanism had not been identified. Here we report the molecular assays on 74 subjects with PTLS-associated duplications, 35 of whom are newly investigated. By both oligonucleotide-based comparative genomic hybridization and recombination hot spot analyses, we identified two cases of the predicted 5 Mb uncommon recurrent PTLS-associated duplication. Interestingly, the crossovers occur in proximity to a recently delineated allelic homologous recombination (AHR) hot spot-associated sequence motif, further documenting the common hot spot features shared between NAHR and AHR. An additional eight subjects with nonrecurrent PTLS duplications were identified. The smallest region of overlap (SRO) for all of the 74 PTLS duplications examined is narrowed to a 125 kb interval containing only RAI1, a gene recently further implicated in autism. Sequence complexities consistent with DNA replication-based mechanisms were identified in four of eight (50%) newly identified nonrecurrent PTLS duplications. Our findings of the uncommon recurrent PTLS-associated duplication at a relative prevalence reflecting the de novo mutation rate and the distribution of 17p11.2 duplication types in PTLS reveal insights into both the contributions of new mutations and the different underlying mechanisms that generate genomic rearrangements causing genomic disorders.

Endogenous viruses: insights into viral evolution and impact on host biology

Abstract: Recent studies have uncovered myriad viral sequences that are integrated or 'endogenized' in the genomes of various eukaryotes. Surprisingly, it appears that not just retroviruses but almost all types of viruses can become endogenous. We review how these genomic 'fossils' offer fresh insights into the origin, evolutionary dynamics and structural evolution of viruses, which are giving rise to the burgeoning field of palaeovirology. We also examine the multitude of ways through which endogenous viruses have influenced, for better or worse, the biology of their hosts. We argue that the conflict between hosts and viruses has led to the invention and diversification of molecular arsenals, which, in turn, promote the cellular co-option of endogenous viruses.

Mechanisms underlying structural variant formation in genomic disorders

Abstract: With the recent burst of technological developments in genomics, and the clinical implementation of genome-wide assays, our understanding of the molecular basis of genomic disorders, specifically the contribution of structural variation to disease burden, is evolving quickly. Ongoing studies have revealed a ubiquitous role for genome architecture in the formation of structural variants at a given locus, both in DNA recombination-based processes and in replication-based processes. These reports showcase the influence of repeat sequences on genomic stability and structural variant complexity and also highlight the tremendous plasticity and dynamic nature of our genome in evolution, health and disease susceptibility.

The complete European guidelines on phenylketonuria: diagnosis and treatment

Abstract: Phenylketonuria (PKU) is an autosomal recessive inborn error of phenylalanine metabolism caused by deficiency in the enzyme phenylalanine hydroxylase that converts phenylalanine into tyrosine. If left untreated, PKU results in increased phenylalanine concentrations in blood and brain, which cause severe intellectual disability, epilepsy and behavioural problems. PKU management differs widely across Europe and therefore these guidelines have been developed aiming to optimize and standardize PKU care. Professionals from 10 different European countries developed the guidelines according to the AGREE (Appraisal of Guidelines for Research and Evaluation) method. Literature search, critical appraisal and evidence grading were conducted according to the SIGN (Scottish Intercollegiate Guidelines Network) method. The Delphi-method was used when there was no or little evidence available. External consultants reviewed the guidelines. Using these methods 70 statements were formulated based on the highest quality evidence available. The level of evidence of most recommendations is C or D. Although study designs and patient numbers are sub-optimal, many statements are convincing, important and relevant. In addition, knowledge gaps are identified which require further research in order to direct better care for the future.

Detection of clinically relevant exonic copy‐number changes by array CGH

Abstract: Array comparative genomic hybridization (aCGH) is a powerful tool for the molecular elucidation and diagnosis of disorders resulting from genomic copy-number variation (CNV). However, intragenic deletions or duplications--those including genomic intervals of a size smaller than a gene--have remained beyond the detection limit of most clinical aCGH analyses. Increasing array probe number improves genomic resolution, although higher cost may limit implementation, and enhanced detection of benign CNV can confound clinical interpretation. We designed an array with exonic coverage of selected disease and candidate genes and used it clinically to identify losses or gains throughout the genome involving at least one exon and as small as several hundred base pairs in size. In some patients, the detected copy-number change occurs within a gene known to be causative of the observed clinical phenotype, demonstrating the ability of this array to detect clinically relevant CNVs with subkilobase resolution. In summary, we demonstrate the utility of a custom-designed, exon-targeted oligonucleotide array to detect intragenic copy-number changes in patients with various clinical phenotypes.