n.

浸透率

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/04/23 11:34:14」(JST)

wiki en

Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene (allele or genotype) that also express an associated trait (phenotype). In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms. For example, if a mutation in the gene responsible for a particular autosomal dominant disorder has 95% penetrance, then 95% of those with the mutation will develop the disease, while 5% will not.

Common examples used to show degrees of penetrance are often highly penetrant. There are several reasons for this:

Highly penetrant alleles, and highly heritable symptoms, are easier to demonstrate, because if the allele is present, the phenotype is generally expressed. Mendelian genetic concepts such as recessiveness, dominance, and co-dominance are fairly simple additions to this principle.
Alleles which are highly penetrant are more likely to be noticed by clinicians and geneticists, and alleles for symptoms which are highly heritable are more likely to be inferred to exist, and then are more easily tracked down.

Associated terminology

complete penetrance. The allele is said to have complete penetrance if all individuals who have the disease-causing mutation have clinical symptoms of the disease.
highly penetrant. If an allele is highly penetrant, then the trait it produces will almost always be apparent in an individual carrying the allele.
incomplete penetrance or reduced penetrance. Penetrance is said to be reduced or incomplete when some individuals fail to express the trait, even though they carry the allele.
low penetrance. An allele with low penetrance will only sometimes produce the symptom or trait with which it has been associated at a detectable level. In cases of low penetrance, it is difficult to distinguish environmental from genetic factors.

Determination

Penetrance can be difficult to determine reliably, even for genetic diseases that are caused by a single polymorphic allele. For many hereditary diseases, the onset of symptoms is age related, and is affected by environmental codeterminants such as nutrition and smoking, as well as genetic cofactors and epigenetic regulation of expression:

Age-related cumulative frequency. Penetrance is often expressed as a frequency, determined cumulatively, at different ages. For example, multiple endocrine neoplasia 1 (MEN 1), a hereditary disorder characterized by parathyroid hyperplasia and pancreatic islet-cell and pituitary adenomas, is caused by a mutation in the menin gene on human chromosome 11q13. In one study the age-related penetrance of MEN1 was 7% by age 10 but increased to nearly 100% by age 60.^[1]
Environmental modifiers. Penetrance may be expressed as a frequency at a given age, or determined cumulatively at different ages, depending on environmental modifiers. For example, several studies of BRCA1 and BRCA2 mutations, associated with an elevated risk of breast and ovarian cancer in women, have examined associations with environmental and behavioral modifiers such as pregnancies, history of breast feeding, smoking, diet, and so forth.
Genetic modifiers. Penetrance at a given allele may be polygenic, modified by the presence or absence of polymorphic alleles at other gene loci. Genome association studies may assess the influence of such variants on the penetrance of an allele.^[2]
Epigenetic regulation. Example ... genomic imprinting by the paternal or maternal allele.

Ascertainment bias

For hereditary hemochromatosis, a disease caused by excess intestinal iron absorption, the degree of penetrance has been a subject of controversy for many years and illustrates the challenges facing investigators seeking a quantitative measure of penetrance. Individuals who are homozygotes for the C282YA allele of the HFE gene are at risk for developing lethal concentrations of iron, particularly in the liver. Typically patients develop clinical disease in late-middle age.^[3]

Determining the penetrance of the C282Y allele can be influenced by when, in the course of a lifetime, homozygotes are evaluated by the medical community. Many of those afflicted do not seek treatment until symptoms are advanced, and with age-related conditions, some individuals die first of other causes. This dilemma is known as an ascertainment bias. There can be a bias favoring only the ascertainment of the most severely affected, or there can be a bias in the other direction, deeming that a homozygote is affected with the disease if they simply have elevated blood iron levels, but no physiological evidence of organ disease such as cirrhosis. Thus a consensus definition of what constitutes the presence of a phenotype is essential for determining the penetrance of an allele.^[4]

Attributable risk

For alleles with incomplete penetrance, the penetrance of the allele is not the same as the attributable risk. For example, many alleles have been shown, through association studies, to cause some form of cancer, often with low penetrance. But cases of the cancer would arise even without the presence of the allele. Attributable risk is that proportion of total risk which can be attributed to the presence of the allele.

Polygenic traits

Most biological traits (such as height or intelligence in humans) are multifactorial, influenced by many genes as well as environmental conditions and epigenetic expression. Only a statistical measure of association is possible with such polygenic traits.

References

^ Bessett JH et al. (Feb 1998). "Characterization of mutations in patients with multiple endocrine neoplasia type 1". American Journal of Human Genetics 62 (2): 232–44. doi:10.1086/301729. PMC 1376903. PMID 9463336.
^ Hughes, David J. (2008-02-19). "Use of association studies to define genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers". Familial Cancer (Springer Netherlands) 7 (3): 233–244. doi:10.1007/s10689-008-9181-0. ISSN 1573-7292. PMID 18283561.
^ Beutler, Ernest (2003-05-01). "Penetrance in hereditary hemochromatosis: The HFE Cys282Tyr mutation as a necessary but not sufﬁcient cause of clinical hereditary hemochromatosis". Blood 101 (9): 3347–3350. doi:10.1182/blood-2002-06-1747. PMID 12707220.
^ KJ Allen, LC Gurrin, CC Constantine, et al. (2008-01-17). "Iron-Overload–Related Disease in HFE Hereditary Hemochromatosis". New England Journal of Medicine 358 (3): 221–230. doi:10.1056/NEJMoa073286. PMID 18199861.

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 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
2. Birt-Hogg-Dubé syndrome birt hogg dube syndrome
3. Congenital central hypoventilation syndrome and other causes of sleep-related hypoventilation in children
4. メンデル遺伝の概要 overview of mendelian inheritance
5. 遺伝性疾患の基本原則 basic principles of genetic disease

English Journal

Update on breast cancer risk prediction and prevention.

Sestak I1, Cuzick J.
Current opinion in obstetrics & gynecology.Curr Opin Obstet Gynecol.2015 Feb;27(1):92-7. doi: 10.1097/GCO.0000000000000153.
PURPOSE OF REVIEW: Breast cancer is the most common cancer in women worldwide. This review will focus on current prevention strategies for women at high risk.RECENT FINDINGS: The identification of women who are at high risk of developing breast cancer is key to breast cancer prevention. Recent findi
PMID 25517358

Exome sequencing reveals mutant genes with low penetrance involved in MEN2A-associated tumorigenesis.

Cai J1, Li L1, Ye L1, Jiang X1, Shen L1, Gao Z1, Fang W1, Huang F1, Su T1, Zhou Y1, Wang W1, Ning G2.
Endocrine-related cancer.Endocr Relat Cancer.2015 Feb;22(1):23-33. doi: 10.1530/ERC-14-0225. Epub 2014 Nov 17.
Activating rearranged during transfection (RET) mutations function as the initiating causative mutation for multiple endocrine neoplasia type 2A (MEN2A). However, no conclusive findings regarding the non-RET genetic events have been reported. This is the first study, to our knowledge, examining geno
PMID 25404689

A novel NKX2-5 loss-of-function mutation predisposes to familial dilated cardiomyopathy and arrhythmias.

Yuan F1, Qiu XB2, Li RG2, Qu XK2, Wang J3, Xu YJ2, Liu X2, Fang WY2, Yang YQ2, Liao DN1.
International journal of molecular medicine.Int J Mol Med.2015 Feb;35(2):478-86. doi: 10.3892/ijmm.2014.2029. Epub 2014 Dec 9.
Dilated cardiomyopathy (DCM) is the most prevalent type of primary myocardial disease, which is the third most common cause of heart failure and the most frequent reason for heart transplantation. Aggregating evidence demonstrates that genetic risk factors are involved in the pathogenesis of idiopat
PMID 25503402

Japanese Journal

QTL Analysis Identifies a Modifier Locus of Aganglionosis in the Rat Model of Hirschsprung Disease Carrying Ednrb^[sl] Mutations

Dang Ruihua,Torigoe Daisuke,Sasaki Nobuya,Agui Takashi
PLoS One 6(11), e27902, 2011-11-22
… Hirschsprung disease (HSCR) exhibits complex genetics with incomplete penetrance and variable severity thought to result as a consequence of multiple gene interactions that modulate the ability of enteric neural crest cells to populate the developing gut. … Moreover, a known HSCR susceptibility gene, Gdnf, was found in QTL that suggested a novel non-coding sequence mutation in GDNF that modifies the penetrance and severity of the aganglionosis phenotype in EDNRB-deficient rats. …
NAID 120003660603

A nonsense mutation in the HOXD13 gene underlies synpolydactyly with incomplete penetrance

Kurban Mazen,Wajid Muhammad,Petukhova Lynn [他]
Journal of human genetics 56(10), 701-706, 2011-10
NAID 40019034084

Related Pictures

★リンクテーブル★

国試過去問	「097I008」
リンク元	「浸透率」「表現率」
拡張検索	「nonpenetrance」

「097I008」

　　[★]

32歳の女性。遺伝相談のために来院した。父が常染色体優性遺伝疾患に罹患している．この疾患の浸透率(penetrance)は50％。近親婚はなく、本人は発症していない。家系図を以下に示す。

第1子が発症する確率はどれか。

a. 1/4
b. 1/8
c. 1/12
d. 1/16
e. 1/24

[正答]

※国試ナビ4※　［097I007］←［国試_097］→［097I009］

「浸透率」

　　[★]

英: penetrance
同: 浸透度、ペネトランス
関: 表現率、表現型

[show details]

浸透度 : 約 265,000 件
浸透率 : 約 401,000 件

あるい遺伝子型をもつ個体中で、表現型に影響を受けた個体の出現頻度

「表現率」

　　[★]

英: penetrance
関: 浸透度、浸透率

「nonpenetrance」

　　[★]

n.

(変異の影響がないこと)非浸透

関: nonpenetrating

[1] Bessett JH et al. (Feb 1998). "Characterization of mutations in patients with multiple endocrine neoplasia type 1". American Journal of Human Genetics 62 (2): 232–44. doi:10.1086/301729. PMC 1376903. PMID 9463336.

[2] Hughes, David J. (2008-02-19). "Use of association studies to define genetic modifiers of breast cancer risk in BRCA1 and BRCA2 mutation carriers". Familial Cancer (Springer Netherlands) 7 (3): 233–244. doi:10.1007/s10689-008-9181-0. ISSN 1573-7292. PMID 18283561.

[3] Beutler, Ernest (2003-05-01). "Penetrance in hereditary hemochromatosis: The HFE Cys282Tyr mutation as a necessary but not sufﬁcient cause of clinical hereditary hemochromatosis". Blood 101 (9): 3347–3350. doi:10.1182/blood-2002-06-1747. PMID 12707220.

[4] KJ Allen, LC Gurrin, CC Constantine, et al. (2008-01-17). "Iron-Overload–Related Disease in HFE Hereditary Hemochromatosis". New England Journal of Medicine 358 (3): 221–230. doi:10.1056/NEJMoa073286. PMID 18199861.

匿名

検索

案内

案内

penetrance