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© 2009 NHS National Genetics Education and DevelopmentCentre

Supporting Genetics Education for Healthwwwgeneticseducationnhsu!

Multifactorial conditions

"his #ower#oint $le contains a num%er of slides that ma& %e useful forteaching of genetics concepts

'ou ma& use these slides and their contents for non(commercial

educational purposes

)ore slides will %e added to this series shortl&


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GENETIC

ENVIRONMENTAL

Duchennemuscular dystrophy

aemophilia

Osteo!enesis imperfecta

Clu" foot#yloric stenosisDislocation of hip

#eptic ulcerDia"etes

Tu"erculosis

#henyl$etonuriaGalactosaemia

%pina "i&daIschaemic heart diseaseAn$ylosin! spondylitis

%cur'y

The contri"utions of !enetic anden'ironmental factors to humandiseases

RareGenetics simple

UnifactorialHigh recurrence rate

CommonGenetics complex MultifactorialLow recurrence rate


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Continuous ()uantitati'e*

characters* #ol&genic + man& genes

* ,arge num%er of genetic factors- each ma!ing onl&a small contri%ution to the $nal phenot&pe


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Multifactorial inheritance

* .nheritance controlled %& man& genes with smalladditive e/ects pol&genic1 plus the e/ects of theenvironment

* Clinical clue 3ne organ s&stem a/ected


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+amily studies of the incidenceof cleft lip (, cleft palate*

The more se'ere the manifestation of a multifactorialcondition- the !reater the pro"a"ility of recurrence


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%ome multifactorial conditions ha'ean une)ual se. ratio

+or some conditions there must "e a di/erent thresholdfor males and females


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+re)uency of pyloric stenosis in relati'es

+or a female to "e a/ected 0ith pyloric stenosis- shemust ha'e a particularly stron! !enetic suscepti"ility


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Multifactorial inheritance1

Factors increasing probability of recurrence in a particular family

* Close relationship to pro%and

* High herita%ilit& of disorder

* #ro%and of more rarel& a/ected se4

* Severe or earl& onset disease

* )ultiple famil& mem%ers a/ected

All these su!!est that the family has a hi!her lia"ility tothe disorder 2 !enes of hi!her e/ect or more ad'erse

en'ironmental in3uences


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Multifactorial inheritance as a mode of

inheritance for a condition is more li$ely if44* Condition is relativel& common

* .ncidence in relatives lower than for single gene disorder %ut higher

than in general population

*5is!s to si%s similar to that of children

* .ncidence falls rapidl& in more distant relatives

* .ncidence in relatives rises as the manifestations %ecome more severe

in the inde4 case

* 5is! to relatives higher when inde4 case is of the least commonl&

a/ected se4* 3%served ris! rises following the %irth of two a/ected children


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Multifactorial traits

* Genetic predisposition li!el& to %e due to a particularcom%ination of genes

* "he genes and environmental factors causing a particular

multifactorial trait ma& var& from person to person


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%ummary

* )ost diseases with a genetic component are not inherited in)endelian fashion %ut displa& multifactorial inheritance

* )ultifactorial disease usuall& pol&genic (man& genes each

with small additive e/ects

* )a6or e/ort to identif& common disease suscepti%ilit& genesunderwa&

* .denti$cation of SN#s associated with disease suscepti%ilit&


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Noof

individuals inpopulation

,ia%ilit&

In multifactorial

disorders- the lia"ilitycur'e is made up of!enetic anden'ironmental factors

Lo0lia"ility

A'era!e

lia"ility

i!hlia"ility


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Noofindividuals inpopulation

Height

Continuous traits 2

"lood pressure- hei!ht


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Noof

individuals inpopulation

,ia%ilit&

In multifactorial

disorders- there is athreshold- a"o'e 0hicha person 0ill de'elopthe multifactorialdisorder


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Noofindividuals inpopulation

,ia%ilit&

In multifactorial disorders- there is athreshold- a"o'e 0hich a person 0illde'elop the multifactorial disorder

"hreshold


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Multifactorial disorders 2 practicepointsCommon conditions

5En'ironmental6 in3uences act 0ith a!enetic predisposition

Multiple !enes 0ith indi'idually smallris$s often implicated

One or!an system a/ected

Recurrence risks:- 5empiric &!ures67 o"tained from population studies

7 use in population from0hich o"tained Noof a/ected

individuals

,ia%ilit& geneticand environmental

factors1

"hreshold

7environment


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Ris$ factors for coronary artery diseaseUncontrollable (but

identiable)

8amil& histor& genetics1ge)ale se4

Potentially controllable ortreatable

8att& diet

H&pertension

Smo!ing

High serum cholesterol

,ow serum HD,

High serum ,D,Stress

.nsu:cient e4ercise

3%esit&

Dia%etes

Ma8or e/ort to identify commondisease suscepti"ility !enesunder0ay


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o0 can the pro"a"ility of recurrence "e

determined for multifactorial disorders9 * "he recurrence risk for multifactorial disorders has to %e

determined through famil& studies

* 3%serve the num%er of a/ected si%lings in man&families (empiric risk)


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o0 e'idence is !athered for !eneticfactors in comple. diseases

* +amilial ris$s

what is the incidence of a disorder in relatives compared with theincidence in the general population;1

* T0in studies

what is the incidence in mono


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Do "oth t0ins sho0 the same characteristic ortrait9

Comparing )=>D= twins can give evidence for genetic and>orenvironmental in?uences

:;


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Determinin! the incidence of a disease in t0inshelps delineate 0hether there are !enetic and

en'ironmental components


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#ro"and %i"lin!s of pro"and

8amilieswith one

child withmultifactor

ialcondition

@0%rothers

andsisters



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@0%rothers

andsisters

2 a/ectedwith

multifactorial

condition

8amilieswith one


ialcondition



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"hereforepro%a%ilit& ofrecurrence A

B>2@ 1

2>@0 a/ected

withmultifactor

ialcondition8amilies

with one


ialcondition


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Common diseases

* Con!enitalmalformationsCleft lip>palateCongenital hip dislocation

Congenital heart defectsNeural tu%e defects#&loric stenosis

"alipes

* Adult onsetdisorders

Dia%etes mellitus

Epileps& Glaucoma H&pertension .schaemic heartdisease

)anic depression Schi


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© 2009 NHS National Genetics Education and Development Supporting Genetics Education for Health

Multifactorial

* E.amples include some cases ofcleft lip and palate neural tu%edefects dia%etes and h&pertension

* Caused "y a com%ination ofgenetic predisposition and

environmental in?uences

* #attern + more a/ected people infamil& than e4pected fromincidence in population %ut doesnFt$t dominant- recessive or (lin!ed

inheritance patterns

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