Trisomy 21 and Down syndrome: a short review

Sommer, Cesar; Henrique-Silva, Flávio

doi:10.1590/s1519-69842008000200031

Cited by 45 publications

(41 citation statements)

References 49 publications

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“…Several genes on chromosome 21 have been identified as DSrelated genes (36,37). For example, a 1.5-fold increase in dosage of DSCR1 and DYRK1A has been shown experimentally to lead to features of the DS phenotype (38).…”

Section: Resultsmentioning

confidence: 99%

“…For example, a 1.5-fold increase in dosage of DSCR1 and DYRK1A has been shown experimentally to lead to features of the DS phenotype (38). Table 1 lists all 40 DBOs from chromosome 21 and 16 candidate DS genes from the literature (36,37). Strikingly, 75% (12/16) of reported DS candidates are also DBOs, whereas under a hypothesis of no association we would expect only two of the candidate genes to also be DBOs; this is a highly significant difference (P = 5.9 × 10 −8 , Fisher's exact test; Table 1).…”

Section: Resultsmentioning

confidence: 99%

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Ohnologs in the human genome are dosage balanced and frequently associated with disease

Makino

McLysaght

2010

Proc. Natl. Acad. Sci. U.S.A.

253

337

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About 30% of protein-coding genes in the human genome are related through two whole genome duplication (WGD) events. Although WGD is often credited with great evolutionary importance, the processes governing the retention of these genes and their biological significance remain unclear. One increasingly popular hypothesis is that dosage balance constraints are a major determinant of duplicate gene retention. We test this hypothesis and show that WGD-duplicated genes (ohnologs) have rarely experienced subsequent small-scale duplication (SSD) and are also refractory to copy number variation (CNV) in human populations and are thus likely to be sensitive to relative quantities (i.e., they are dosage-balanced). By contrast, genes that have experienced SSD in the vertebrate lineage are more likely to also display CNV. This supports the hypothesis of biased retention of dosage-balanced genes after WGD. We also show that ohnologs have a strong association with human disease. In particular, Down Syndrome (DS) caused by trisomy 21 is widely assumed to be caused by dosage effects, and 75% of previously reported candidate genes for this syndrome are ohnologs that experienced no other copy number changes. We propose the remaining dosage-balanced ohnologs on chromosome 21 as candidate DS genes. These observations clearly show a persistent resistance to dose changes in genes duplicated by WGD. Dosage balance constraints simultaneously explain duplicate gene retention and essentiality after WGD. E arly in the vertebrate lineage the genome of our simple ancestor experienced radical upheaval from two rounds of whole genome duplication (WGD) and the subsequent chromosomal rearrangement and loss of many of the duplicate copies ("ohnologs") (1-3). Although only about 20-30% of the protein-coding genes in the human genome can be traced back to these events (ref. 3 and this study), the two tetraploid episodes in vertebrate history have frequently been credited with creating the conditions for the evolution of vertebrate complexity. Understanding the patterns of ohnolog retention is crucial to develop a unified model for the evolutionary impact of WGD and many groups have uncovered significant trends such as enrichment for developmental genes (4-6) and protein complex membership (7).Recently it was shown that mammalian ohnologs are more essential (i.e., knockout of one copy is more likely to lead to sterility or inviability) than paralogs generated by small-scale duplication (SSD) and are equally as essential as singleton genes (7). A prevalence of dosage-balanced genes among ohnologs was proposed to explain this contradiction of the theoretical, expected backup role of duplicated genes, which should buffer against such effects. Dosage balance may exist between two or more genes whose products interact or participate in the same pathway or process (8-10). According to the dosage balance hypothesis, changes in the relative dosage of gene product, such as would occur through duplication of some but not all of the balanced gene set, should...

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Ohnologs in the human genome are dosage balanced and frequently associated with disease

Makino

McLysaght

2010

Proc. Natl. Acad. Sci. U.S.A.

253

337

View full text Add to dashboard Cite

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“…In the case of trisomy 21, increased gene dosage, attributable to an extra copy of HSA21, appears to result in an increase in gene expression for a number of HSA21 genes. 19,20 Because trisomy 21 significantly decreases the odds of ROP, HSA21 may include a set of genes that targets ROP protection. Indeed, at least 3 proteins encoded by HSA21 genes (endostatin, superoxide dismutase, and regulator of calcineurin 1 [RCAN 1]) are already independently being investigated as either antiangiogenic agents or as potential ROP protectants.…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, at least 3 proteins encoded by HSA21 genes (endostatin, superoxide dismutase, and regulator of calcineurin 1 [RCAN 1]) are already independently being investigated as either antiangiogenic agents or as potential ROP protectants. 10,19,21 Endostatin has been shown to inhibit endothelial cell proliferation, migration, and retinal angiogenesis in vitro and in vivo. 22,23 Superoxide dismutase, an essential enzyme in the metabolism of free radicals, has been shown to ameliorate oxygen-induced retinopathy in transgenic mice.…”

Section: Discussionmentioning

confidence: 99%

Trisomy 21 and Risk of Retinopathy of Prematurity

Movsas¹,

Spitzer

Gewolb

2015

Pediatrics

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“…This is the most common cause of mental impairment and determines the trend to pathological expression of brain structure and function in people with this syndrome (Agulló & González, 2006;Sommer & Henrique-Silva, 2008;Torquato, Lança, Pereira, Carvalho, & Silva, 2013). This information is also regulated by other genes of the individual, so that the variability observed between people with DS is notable.…”

Section: Introductionmentioning

confidence: 99%

<b>Electromyographic evaluation of the lower limbs of patients with Down syndrome in hippotherapy

Ribeiro

Espíndula

Ferreira

et al. 2017

Acta Sci. Health Sci.

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ABSTRACT. Hippotherapy is a therapeutic method that uses the horse's movement to achieve functional results in practitioners with Down syndrome (DS), who present motor and neurophysiological changes that affect the musculoskeletal system. Evaluating the motor behavior related to the control and the improvement of muscle activation in practitioners with Down syndrome subjected to hippotherapy. 10 practitioners were divided into two groups: Down Group (DG) -practitioners with DS, and Healthy Group (HG) -practitioners with no physical impairment. The muscles gluteus medius, tensor fasciae latae, rectus femoris, vastus medialis, vastus lateralis, biceps femoris, tibialis anterior and gastrocnemius were evaluated by electromyography using gross RMS values, which correspond to muscle activation; the evaluations were performed on the 1 st and 10 th hippotherapy sessions (frequency: once a week), and after 2 months interval without treatment, they were performed on the 1 st and 10 th hippotherapy sessions (frequency: twice a week). It was noted that activation of the studied muscles increased with the passing of sessions, regardless the weekly frequency of attendance; however, the period without treatment resulted in reduction of this effect. Practitioners with DS presented satisfactory changes in muscle activation pattern, in learning and in motor behavior during hippotherapy sessions.Keywords: muscle activation, electromyography, hippotherapy, Down syndrome, equine assisted therapy.Avaliação eletromiográfica dos membros inferiores de pacientes com síndrome de Down na equoterapia RESUMO. Equoterapia é um método terapêutico que utiliza o movimento do cavalo para alcançar resultados funcionais, realizada em praticantes com síndrome de Down (SD), que apresentam alterações neurofisiológicas e motoras que afetam o sistema musculoesquelético. Avaliar o comportamento motor relacionado ao controle e melhora a ativação muscular em praticantes com SD submetidos ao tratamento equoterapêutico. Participaram dez praticantes divididos em dois grupos: grupo Down (GD) -praticantes com SD, e grupo Saudável (GS) -praticantes sem comprometimento físico. Os músculos glúteo médio, tensor da fáscia lata, reto femoral, vasto medial, vasto lateral, bíceps femoral, tibial anterior e gastrocnêmio foram avaliados por meio da eletromiografia, utilizando o valor de RMS bruto que corresponde à ativação muscular, e as avaliações foram realizadas na primeira e décima sessões de equoterapia (frequência: 01 vez por semana); e após intervalo de dois meses sem tratamento, foi realizada na primeira e décima sessões de equoterapia (frequência: 02 vezes por semana). Observou-se que a ativação muscular dos músculos estudados aumentou com o passar das sessões, independente da frequência semanal de atendimento; mas o período sem tratamento resultou em redução deste efeito. Os praticantes com SD apresentaram mudanças satisfatórias no padrão de ativação muscular, na aprendizagem e no comportamento motor no decorrer das sessões de equoterapia.Palavras-chave: ativa...

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Trisomy 21 and Down syndrome: a short review

Cited by 45 publications

References 49 publications

Ohnologs in the human genome are dosage balanced and frequently associated with disease

Ohnologs in the human genome are dosage balanced and frequently associated with disease

Trisomy 21 and Risk of Retinopathy of Prematurity

<b>Electromyographic evaluation of the lower limbs of patients with Down syndrome in hippotherapy

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