WordNet

anticipating with confidence of fulfillment (同)expectation
an expectation (同)expectancy
something expected (as on the basis of a norm); "each of them had their own anticipations"; "an indicator of expectancy in development" (同)expectancy
pertaining to or referring to origin; "genetic history reconstructs the origins of a literary work"
of or relating to the science of genetics; "genetic research" (同)genetical
the branch of biology that studies heredity and variation in organisms (同)genetic science
agile Old World viverrine having a spotted coat and long ringed tail (同)Genetta genetta

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(…の)予想,期待《+『of』+『名』》,(…という)予想《+『that節』》
遺伝学

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2014/05/11 10:38:28」(JST)

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In genetics, anticipation is a phenomenon whereby the symptoms of a genetic disorder become apparent at an earlier age as it is passed on to the next generation. In most cases, an increase of severity of symptoms is also noted. Anticipation is common in trinucleotide repeat disorders such as Huntington's disease and myotonic dystrophy where a dynamic mutation in DNA occurs. All of these diseases have neurological symptoms. Prior to the understanding of the genetic mechanism for anticipation, it was debated whether anticipation was a true biological phenomenon or whether the earlier age of diagnosis was related to heightened awareness of disease symptoms within a family.

Trinucleotide repeats and expansion

Trinucleotide repeats are apparent in a number of loci in the human genome. They have been found in introns, exons and 5' or 3' UTR's. They consist of a pattern of three nucleotides (e.g. CGG) which is repeated a number of times. During meiosis, unstable repeats can undergo triplet expansion (see later section); in this case, the germ cells produced have a greater number of repeats than are found in the somatic tissues.

The mechanism behind the expansion of the triplet repeats is not well understood. One hypothesis is that the increasing number of repeats influence the overall shape of the DNA, which can have an effect on its interaction with DNA polymerase and thus the expression of the gene.^{[citation needed]}

Disease mechanisms

For many of the loci, trinucleotide expansion is harmless,^{[citation needed]} but in some areas expansion has detrimental effects that cause symptoms. When the trinucleotide repeat is present within the protein-coding region, the repeat expansion leads to production of a mutant protein with gain of function. This is the case for Huntington's disease, where the trinucleotide repeat encodes a long stretch of glutamine residues. When the repeat is present in an untranslated region, it could affect the expression of the gene in which the repeat is found (ex. fragile X) or many genes through a dominant negative effect (ex. myotonic dystrophy).

In order to have a deleterious effect, the number of repeats must cross a certain threshold. For example, normal individuals have between 5 and 30 CTG repeats within the 3' UTR of DMPK, the gene that is altered in myotonic dystrophy. If the number of repeats becomes greater than 50, the person is only mildly affected – perhaps having only cataracts. However, meiotic instability could result in a dynamic mutation that increases the number of repeats in offspring inheriting the mutant allele. Once the number of copies reaches over 100, the disease will manifest earlier in life (although the individual will still reach adulthood before the symptoms are evident) and the symptoms will be more severe – including electrical myotonia. As the number progresses upwards past 400, the symptoms show themselves during childhood or infancy.

Examples of diseases showing anticipation

Diseases showing anticipation include:

Autosomal Dominant
- Several spinal cerebellar ataxias
- Huntington's Disease – CAG
- Myotonic Dystrophy – CTG
- dyskeratosis congenita – TTAGGG (telomere repeat sequence)^[1]

Autosomal Recessive
- Friedreich Ataxia – GAA (Note: Friedreich ataxia does not usually exhibit anticipation because it is an autosomal recessive disorder.^[2])

X-Linked
- Fragile X syndrome – CGG

Without Expression Type
- Crohn's disease^[3]
- Behçet's disease^[4]

References

^ Armanios, M., J. L. Chen, Y. P. Chang, R. A. Brodsky, A. Hawkins, C. A. Griffin, J. R. Eshleman, A. R. Cohen, A. Chakravarti, A. Hamosh, and C. W. Greider. 2005. Haploinsufficiency of telomerase reverse transcriptase leads to anticipation in autosomal dominant dyskeratosis congenita. Proc Natl Acad Sci U S A 102(44):15960-4.
^ Link text, NCBI Bookshelf: Friedreich Ataxia.
^ Polito, J.M.; A.I Mendeloff, M.L Harris, T.M Bayless, Barton Childs, R.C Rees (23 March 1996). "Preliminary evidence for genetic anticipation in Crohn's disease". The Lancet 347 (9004): 798–800. doi:10.1016/S0140-6736(96)90870-3. Cite uses deprecated parameters (help); |accessdate= requires |url= (help)
^ Fresko, I; M Soy, V Hamuryudan, S Yurdakul, Ş Yavuz, Z Tümerd, H Yazici (1998). "Genetic anticipation in Behçet’s syndrome". Ann Rheum Dis 57: 45–48. doi:10.1136/ard.57.1.45. Cite uses deprecated parameters (help); |accessdate= requires |url= (help)

External links

Anticipation.info
Genetic anticipation at the US National Library of Medicine Medical Subject Headings (MeSH)

UpToDate Contents

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1. 遺伝性疾患の基本原則 basic principles of genetic disease
2. ハンチントン病：遺伝学と病因 huntington disease genetics and pathogenesis
3. 単一遺伝子性疾患の非メンデル遺伝のパターン non mendelian inheritance patterns of monogenic diseases
4. メンデル遺伝の概要 overview of mendelian inheritance
5. 成人における医療手技に対する急性不安発作：経過、スクリーニング、評価、および
鑑別診断 acute procedure anxiety in adults course screening assessment and differential diagnosis

English Journal

Repeat interruptions in spinocerebellar ataxia type 10 expansions are strongly associated with epileptic seizures.

McFarland KN, Liu J, Landrian I, Zeng D, Raskin S, Moscovich M, Gatto EM, Ochoa A, Teive HA, Rasmussen A, Ashizawa T.Author information Department of Neurology, University of Florida, Gainesville, FL, 32610, USA.AbstractSpinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilepsy. SCA10 expansions containing penta- and heptanucleotide interruption motifs, termed "ATCCT interruptions," experience large contractions during germline transmission, particularly in paternal lineages. At the same time, these alleles confer an earlier age at onset which contradicts traditional rules of genetic anticipation in repeat expansions. Previously, ATCCT interruptions have been associated with a higher prevalence of epileptic seizures in one Mexican-American SCA10 family. In a large cohort of SCA10 families, we analyzed whether ATCCT interruptions confer a greater risk for developing seizures in these families. Notably, we find that the presence of repeat interruptions within the SCA10 expansion confers a 6.3-fold increase in the risk of an SCA10 patient developing epilepsy (6.2-fold when considering patients of Mexican ancestry only) and a 13.7-fold increase in having a positive family history of epilepsy (10.5-fold when considering patients of Mexican ancestry only). We conclude that the presence of repeat interruptions in SCA10 repeat expansion indicates a significant risk for the epilepsy phenotype and should be considered during genetic counseling.
Neurogenetics.Neurogenetics.2013 Dec 7. [Epub ahead of print]
Spinocerebellar ataxia type 10 (SCA10), an autosomal dominant neurodegenerative disorder, is the result of a non-coding, pentanucleotide repeat expansion within intron 9 of the Ataxin 10 gene. SCA10 patients present with pure cerebellar ataxia; yet, some families also have a high incidence of epilep
PMID 24318420

Infantile Onset Spinocerebellar Ataxia 2 (SCA2): A Clinical Report With Review of Previous Cases.

Singh A, Faruq M, Mukerji M, Dwivedi MK, Pruthi S, Kapoor S.Author information 1Pediatric Research and Genetic Lab, MAMC Associated Lok Nayak Hospital, New Delhi, India.AbstractAutosomal dominant cerebellar ataxia type I is a heterogenous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with different pathogenic loci, specifically spinocerebellar ataxia 1 (6p24-p23), spinocerebellar ataxia 2 (12q24.1), and spinocerebellar ataxia 3 (14q32.1). The shared pathogenic mutational event is the expansion of the CAG repeat that results in polyglutamine extended stretches in the encoded proteins. CAG repeat disorders generally show the phenomenon of anticipation, which is more often associated with paternal transmission. In this report, we describe a patient with infantile-onset spinocerebellar ataxia type 2 (∼320 CAG repeat) who inherited the disease from his father (47 CAG repeats). We have summarized the clinical, neuroimaging, electroencephalographic (EEG), and molecular data of previous cases and attempt to highlight the most consistent findings. Our intent is to help treating clinicians to suspect this disorder and to offer timely genetic counseling for a currently potentially untreatable disorder.
Journal of child neurology.J Child Neurol.2013 Dec 2. [Epub ahead of print]
Autosomal dominant cerebellar ataxia type I is a heterogenous group of spinocerebellar ataxias with variable neurologic presentations, with age of onset varying from infancy to adulthood. Autosomal dominant cerebellar ataxia type I is composed mainly of 3 prevalent spinocerebellar ataxia types with
PMID 24300164

Non-telomeric epigenetic and genetic changes are associated with the inheritance of shorter telomeres in mice.

Roberts AR, Huang E, Jones L, Daxinger L, Chong S, Whitelaw E.Author information Queensland Institute of Medical Research, Herston, QLD, Australia.AbstractStudies using human and mouse cells have revealed some changes to non-telomeric chromatin and gene expression in response to abnormally short telomeres. To investigate this further, we studied the effect of inheriting shorter telomeres on transcription and genetic stability at non-telomeric sites in the mouse. Using multiple generations of Terc knockout mice, we show that inheriting shorter telomeres from one parent increases the likelihood of transcriptional silencing at a non-telomeric green fluorescent protein (GFP) transgene inherited from the other parent. In these cases, silencing must occur at or after zygote formation. In grand-offspring from a G3 Terc (-/-) parent, transgene expression was further reduced and associated with increased DNA methylation and, surprisingly, reduced copy number at the transgene array. In these cases, the transgene had been passed through the germline of a Terc-compromised parent, providing an opportunity for meiotic events. Furthermore, genome-wide microarray analysis of copy number variations revealed greater genetic instability in G3 Terc (-/-) mice than detected in wild-type mice of the same genetic background. Our results have implications for the molecular mechanisms underlying premature-ageing syndromes, such as dyskeratosis congenita. In autosomal-dominant dyskeratosis congenita, progressive telomere shortening is seen as it passes down the generations, and this is associated with anticipation, i.e. the disease becomes more severe earlier. The underlying mechanism is not known, but has been considered to be simply associated with decreases in telomere length. Epigenetic and/or genetic changes at non-telomeric regions could, in theory, be involved.
Chromosoma.Chromosoma.2013 Dec;122(6):541-54. doi: 10.1007/s00412-013-0427-8. Epub 2013 Jul 18.
Studies using human and mouse cells have revealed some changes to non-telomeric chromatin and gene expression in response to abnormally short telomeres. To investigate this further, we studied the effect of inheriting shorter telomeres on transcription and genetic stability at non-telomeric sites in
PMID 23864360

Japanese Journal

Rooting "Ko-ko-ro" into the Brain: Toward the Neuroanatomy of Mind

Mori Nozomu
Acta medica Nagasakiensia 50(3), 83-91, 2005-09
… The current understanding of the mechanism of mind is limited, but growing evidence suggests that molecular, cellular, genetic, psychological, cognitive, and system neurobiological methods could help to further our knowledge of the mind. … In this review, I will overview current understanding of the components of mind, particularly from a molecular neurobiological perspective, with anticipation that mapping the mind anatomically in molecular terms may ultimately be possible in the human brain. …
NAID 110001790513

遺伝的アルゴリズムとファジィ評価を用いた物資配送計画

前田幹夫,濱田薫,村上周太
知能と情報 : 日本知能情報ファジィ学会誌 : journal of Japan Society for Fuzzy Theory and Intelligent Informatics 15(1), 111-126, 2003-02-15
実際の物資配送においては,得意先間の移動時間が移動する時間帯によって変化することから,本論文では,総配送時間の最小化だけでなく,企業活動において複数の得意先に物資を配送してまわる際に,効率的な配送経路を特定し,各得意先得意先への到着時間指定や配送順序の制約条件も考慮する.その条件のもとで総巡回時間や到着時刻をファジィ数で表し,ファジィ評価することによって配送経路の決定を行う.この決定において,ベス …
NAID 110002690814