Kondisi multifaktorial
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Transcript of Kondisi multifaktorial
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Multifactorial conditions
"his #ower#oint $le contains a num%er of slides that ma& %e useful forteaching of genetics concepts
'ou ma& use these slides and their contents for non(commercial
educational purposes
)ore slides will %e added to this series shortl&
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
GENETIC
ENVIRONMENTAL
Duchennemuscular dystrophy
aemophilia
Osteo!enesis imperfecta
Clu" foot#yloric stenosisDislocation of hip
#eptic ulcerDia"etes
Tu"erculosis
#henyl$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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
+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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
%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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
+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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
%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$cation of SN#s associated with disease suscepti%ilit&
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Noof
individuals inpopulation
,ia%ilit&
In multifactorial
disorders- the lia"ilitycur'e is made up of!enetic anden'ironmental factors
Lo0lia"ility
A'era!e
lia"ility
i!hlia"ility
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Noofindividuals inpopulation
Height
Continuous traits 2
"lood pressure- hei!ht
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Noof
individuals inpopulation
,ia%ilit&
In multifactorial
disorders- there is athreshold- a"o'e 0hicha person 0ill de'elopthe multifactorialdisorder
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Noofindividuals inpopulation
,ia%ilit&
In multifactorial disorders- there is athreshold- a"o'e 0hich a person 0illde'elop the multifactorial disorder
"hreshold
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Multifactorial disorders 2 practicepointsCommon conditions
5En'ironmental6 in3uences act 0ith a!enetic predisposition
Multiple !enes 0ith indi'idually smallris$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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Do "oth t0ins sho0 the same characteristic ortrait9
Comparing )=>D= twins can give evidence for genetic and>orenvironmental in?uences
:;
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
Determinin! the incidence of a disease in t0inshelps delineate 0hether there are !enetic and
en'ironmental components
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
#ro"and %i"lin!s of pro"and
8amilieswith one
child withmultifactor
ialcondition
@0%rothers
andsisters
#ro"and %i"lin!s of pro"and
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
#ro"and %i"lin!s of pro"and
@0%rothers
andsisters
2 a/ectedwith
multifactorial
condition
8amilieswith one
child withmultifactor
ialcondition
#ro"and %i"lin!s of pro"and
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
#ro"and %i"lin!s of pro"and
"hereforepro%a%ilit& ofrecurrence A
B>2@ 1
2>@0 a/ected
withmultifactor
ialcondition8amilies
with one
child withmultifactor
ialcondition
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© 2009 NHS National Genetics Education and DevelopmentCentre
Supporting Genetics Education for Healthwwwgeneticseducationnhsu!
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