genetic variability
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Journal of allergy and clinical immunology, ISSN 0091-6749 vol. 115, no. 4, suppl., April 2005
S. 525-545 : il. ; 28 cm
Zvýšené hladiny lipoproteinu(a) jsou považovány za nezávislý rizikový faktor v procesu aterogeneze. Strukturní i funkční charakteristika částice lipoproteinu(a) je určena přítomností apolipoproteinu(a). Přestože jsou plazmatické hladiny tohoto lipoproteinu téměř zcela pod genetickou kontrolou genu pro apolipoprotein(a), vykazují značnou populační variabilitu. Velká část této variability je způsobena délkovým polymorfizmem genu pro apolipoprotein(a). Zbývající variabilita může být dána jak přítomností sekvenčních polymorfizmů v kódující sekvenci zmíněného genu, tak v jeho regulačních elementech. V kódující oblasti genu pro apolipoprotein(a) bylo zatím odhaleno jen málo polymorfních variant s funkčním významem. Rovněž analýza tří oblastí schopných regulovat expresi genu (promotor, zesilovače DHII a DHIII) prokázala nižší variabilitu, než se očekávalo. I přes dominantní úlohu jediného genu je genetická determinace hladin Lp(a) velice komplexní. Hlavní úlohu zde hraje délkový polymorfizmus genu pro apolipoprotein(a) a celá řada sekvenčních variant ovlivňujících jeho expresi a efektivitu tvorby lipoproteinové částice. Svou roli mají pravděpodobně i další genetické lokusy s minoritním účinkem a modulace negenetickými faktory.
Increased levels of lipoprotein(a) are supposed to be an independent risk factor for atherosclerosis. Apolipoprotein(a) determines structural and functional characteristics of the lipoprotein particle. The lipoprotein(a) concentration is almost entirely genetically determined at the apolipoprotein(a) gene locus, nevertheless it varies widely between individuals in all populations studied so far. Large part of the variance is correlated to the apolipoprotein(a) gene length polymorphism. Some of the variance could be additionally related to polymorphic sites either in the coding sequence or in the transcription regulatory regions. Only a few functional variants were discovered in the coding sequence of apolipoprotein(a) gene so far. Moreover, analyses of relevant regulatory regions (promoter, DHII and DHIII enhancers) have revealed less variability than was expected. Despite the lipoprotein(a) levels are under dominant control of a single locus its genetic determination is quite complex. The basic role belongs to the apolipoprotein(a) gene length polymorphism and to a panel of sequence variants affecting apolipoprotein(a) gene expression and lipoprotein(a) particle production rate. Besides, minor impact of other locuses and modulation by non–genetic factors should be considered.
- MeSH
- buněčné jádro MeSH
- genetická transkripce MeSH
- hormony štítné žlázy fyziologie MeSH
- onkogenní proteiny MeSH
- Publikační typ
- přehledy MeSH
BACKGROUND: Quest for understanding the nature of mechanisms governing the life span of clonal organisms lasts for several decades. Phylogenetic evidence for recent origins of most clones is usually interpreted as proof that clones suffer from gradual age-dependent fitness decay (e.g. Muller's ratchet). However, we have shown that a neutral drift can also qualitatively explain the observed distribution of clonal ages. This finding was followed by several attempts to distinguish the effects of neutral and non-neutral processes. Most recently, Neiman et al. 2009 (Ann N Y Acad Sci.:1168:185-200.) reviewed the distribution of asexual lineage ages estimated from a diverse array of taxa and concluded that neutral processes alone may not explain the observed data. Moreover, the authors inferred that similar types of mechanisms determine maximum asexual lineage ages in all asexual taxa. In this paper we review recent methods for distinguishing the effects of neutral and non-neutral processes and point at methodological problems related with them. RESULTS AND DISCUSSION: We found that contemporary analyses based on phylogenetic data are inadequate to provide any clear-cut answer about the nature and generality of processes affecting evolution of clones. As an alternative approach, we demonstrate that sequence variability in asexual populations is suitable to detect age-dependent selection against clonal lineages. We found that asexual taxa with relatively old clonal lineages are characterised by progressively stronger deviations from neutrality. CONCLUSIONS: Our results demonstrate that some type of age-dependent selection against clones is generally operational in asexual animals, which cover a wide taxonomic range spanning from flatworms to vertebrates. However, we also found a notable difference between the data distribution predicted by available models of sequence evolution and those observed in empirical data. These findings point at the possibility that processes affecting clonal evolution differ from those described in recent studies, suggesting that theoretical models of asexual populations must evolve to address this problem in detail. REVIEWERS: This article was reviewed by Isa Schön (nominated by John Logsdon), Arcady Mushegian and Timothy G. Barraclough (nominated by Laurence Hurst).
- MeSH
- biologická evoluce MeSH
- genetická variace genetika MeSH
- nepohlavní rozmnožování MeSH
- populační genetika metody MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Všeobecnou charakteristikou všetkých biologických systémov sú ich vlastné biologické rytmy a biologická variabilita. Táto variabilita je podmienená viacerými faktormi, ktoré je možné rozdeliť na faktory vnútorné a faktory vonkajšie. Genetické faktory a faktory vonkajšieho prostredia navzájom interferujú a vzájomne sa ovplyvňujú. Ich výslednými prejavmi je potom variabilita prejavov a činností celého živého organizmu. Predkladaný prehľad rozoberá fakty, ktoré sú dôležité z prognostického hľadiska a pre stanovenie globálneho kardiovaskulárneho rizika pacienta.
All biological systems share the common characteristic of having biological rhythms and variability. This variability is determined by several factors, which can be categorised as intrinsic and extrinsic factors. Genetic and environmental factors interact with and influence one another. This results in the variability of expressions and actions of the living organism as a whole. This overview discusses those facts that are of importance in terms of the prognosis and for determining a patient’s global cardiovascular risk.
- MeSH
- ateroskleróza prevence a kontrola MeSH
- cholesterol krev MeSH
- dyslipidemie diagnóza farmakoterapie krev MeSH
- lidé MeSH
- polymorfismus genetický MeSH
- prognóza MeSH
- rizikové faktory MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- přehledy MeSH
Bežná variabilná imunodeficiencia je heterogénnou skupinou ochorení, ktoré spája podobný laboratórny nález v imunoprofile. Hoci ide o prevažne protilátkovú poruchu imunity, zmeny a odchýlky nachádzame aj v oblasti celulárnej imunity. Diagnostické kritériá a klasifikačné systémy zatiaľ nie sú schopné stanoviť klinicky plne využiteľné fenotypové rozdelenie pacientov. V tejto problematike by mohla kľúčovú úlohu zohrať genotypová klasifikácia. Zoznam kauzálnych génov pre vznik ochorenia sa neustále rozširuje. Mutácie v známych génoch sa ale potvrdia len u približne 10–25 % pacientov. Aj tieto nálezy je potrebné správne interpretovať, čo je často značne komplikované. Medzi ďalšie zvažované príčinné faktory vzniku patria epigenetické zmeny, oligogénna a polygénna dedičnosť alebo vplyv vonkajšieho prostredia.
Common variable immunodeficiency is heterogeneous group of disorders that belongs to primary immunodeficiency disorders. Combined defect of humoral and cellular immunity is the main sign. Diagnostic criteria and classification are still insufficient for optimal clinical use. This problem can be solved by genotype classification. There are many causal genes but these are found only in 10 % to 25 % of the patients. Moreover, these findings have to be interpreted correctly, which is complicated. Other possible causes are epigenetics, oligogenic, polygenic inheritance and environmental factors.
Diabetes mellitus, especially when complicated with decline of renal function due to diabetic nephropathy (DN), is associated with accumulation of advanced glycation end products (AGEs) exerting their adverse effects via receptor of AGE (RAGE). Soluble RAGE (sRAGE) is a truncated form of RAGE functioning as an inhibitor of AGE-mediated signalling. We studied relationships between sRAGE, renal function and genetic variability in the AGER gene in diabetic subjects. Study comprised a total of 265 diabetics (type 1 or 2 or LADA) with normoalbuminuria (n = 94) or DN (n = 171). sRAGE (assessed by ELISA) was significantly higher in DN than normoalbuminuria subjects (P = 0.007) and positively correlated with age, S-urea, S-creatinine and albuminuria and AGEs (determined spectrofluorimetrically), negatively with GFR (all P < 0.05); however, multivariate regression revealed that GFR was the only independent variable associated with sRAGE (P = 0.047). sRAGE did not correspond with carrier state of risk-haplotype copies (RAGE2) (P > 0.05). In conclusion, GFR is a principal determinant of sRAGE concentration and gradual sRAGE increase in subjects with advancing impairment of renal function is paralleled by AGEs.
- MeSH
- diabetické nefropatie genetika patofyziologie MeSH
- ELISA MeSH
- financování organizované MeSH
- genetická variace MeSH
- haplotypy MeSH
- hodnoty glomerulární filtrace MeSH
- lidé středního věku MeSH
- lidé MeSH
- produkty pokročilé glykace krev MeSH
- průřezové studie MeSH
- receptory imunologické genetika MeSH
- senioři MeSH
- Check Tag
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- senioři MeSH
- ženské pohlaví MeSH
