1,721,271 research outputs found
Genomic architecture and chromosome rearrangements
No full textAn increasing number of human diseases are recognized to result from recurrent DNA rearrangements involving unstable genomic regions. These are termed genomic disorders, in which the clinical phenotype is a consequence of abnormal dosage of gene(s) located within the rearranged genomic fragments. Both inter- and intrachromosomal rearrangements are facilitated by the presence of region-specific low-copy repeats (LCRs) and result from nonallelic homologous recombination (NAHR) between paralogous genomic segments. LCRs usually span approximately 10-400 kb of genomic DNA, share >or= 97% sequence identity, and provide the substrates for homologous recombination, thus predisposing the region to rearrangements
Regional assignment of the gene coding for a human Graves' disease autoantigen to 10q21.3-q22.1
No full textPatologia ereditaria da gain of function
No full textGain of function variations may lead to enhancement of existing protein function (hyper-
morph) or to acquisition of novel and possibly abnormal biological activities (neomorph).
Point mutations, chromosomal rearrangements and copy number amplifcations are common mechanisms that exert a gain of function effect in several human diseases, such as
cancer or rare developmental syndromes. Traditionally, “gain of function” and “loss of function” are considered as the antithetical functional effects of a particular genetic variation.
Accordingly, gain of function mutations may be associated with highly heterogeneous
phenotypical manifestations of the disease or even completely distinct clinical conditions
when compared to loss of function variations in the same gene. However, this dichotomic
scenario has become less cogent in the last decade with the evidence that both mutation types, when present in the same gene, may result in strikingly similar phenotypic
outcomes. Such is the paradigmatic case of TP53, which may promote tumourigenesis
after accumulation of both hypomorph and neomorph mutations. Importantly, many other
factors, such as tissue type and genetic background, may also influence the phenotype.
In the last few years, novel pathogenic mechanisms associated with gain of function
variations have emerged, including the formation of new chromatin domains, also known
as neo-TADs (Topologically Associated Domains), as a result of genomic duplications.
Importantly, many innovative personalised therapies take advantage of the specifc targeting of gain of function variations through different strategies, such as enzymatic inhibition,
RNA interference or targeted genome editing, suggesting the implementation of these
therapeutic approaches in the near futur
Scotosensitive and photosensitive myoclonic seizures in an infant with trisomy 13.
No full textWe describe a male carrier of trisomy 13 with scotosensitive and photosensitive myoclonic seizures appearing at the age of 8 months and persisting until death at 20 months. The seizures consisted of massive myoclonic jerks induced both by switching the room light suddenly on or off or by IPS with a frequency of 1 s. Spontaneous seizures were absent. The child also presented from the same age with breath-holding spells. This is interesting because it represents a rare example of the co-occurrence of scotosensitive and photosensitive seizures. Furthermore, a possible association to locus on 13q31.3 has been reported for photosensitivity, while for scotosensitivity there is no previous genetic informatio
Inversion Chromosomes
No full textA number of findings revealed that chromosome inversions are more frequent than deduced from classical cytogenetic studies. Indeed, some paracentric cryptic inversions have been found to be flanked by segmental duplications, either causing a Mendelian disease owing to
the interruption of specific genes at inversion breakpoints or being present in the normal population as a polymorphism. In the latter case, in the heterozygous state they predispose to further unbalanced rearrangements such as inv dup rearrangements or simple deletions and
duplications. The importance of this susceptibility factor has been well clarified with respect to some genomic disorders involving chromosome 8p and it is now emerging as a possible model that may explain the genetic basis of other recurrent chromosome rearrangements
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