Pedigreeanalysis

Analysisofinheritanceinhumanfamilies
Averyimportanttoolforstudyinghumaninherited
diseases
Allowinferencesconcerninggenotypesinafamilyorpopulation
Allowspredictionsconcerningphenotypesofoffspringinheritinga
geneticdisease(geneticcounseling)
Typicallysmallnumberofoffspring
Mendelianratiosrarelyobserved
thismeansthenormal3:1dominanttorecessiveratio
doesntusuallyoccur.
Mostcommonsymbolsusedincreating
apedigree

unaffected unaffected affected affected

male female male female
 Othercommon
signsandsymbols
usedinpedigree
analysis
Samplepedigreecysticfibrosis
male female

affectedindividuals

Theromannumeralsindicatethegeneration(I,IIorIII)and
thenumbersshowbirthorderofchildren(1,2,3,4etc.)
Basedonthesamepedigree,wecandetermineareasonableguess
astowhatthegenotypesoftheparentsandoffspringare:
Assumingthisisarecessivegene,
weknowthatII3andIII4mustbe
aa.
Thereforebothparentsofthese
offspringmusthavegivenana
allele.
So,I1,I2,II4andII5musteach
haveoneaintheirgenotypes.
SinceI1,I2,II4andII5dont
havethedisease,theirotherallele
mustbeA.
Alltherestofthepeoplecouldbe
eitherAAorAa.
 I1 I2

II1 II3 II5

II2 II4

1. Whatarethegenotypesorpossiblegenotypesforeach
individualinthisfamily?
2. UsetheletterBtorepresentdominantallelesandbto
representrecessivealleles.
 Categoriesofinheritance
Autosomalmeansinheritedonchromosome122whilesex
linkedmeansinheritedoneitherXorYchromosome.
Autosomalrecessive
e.g.,PKU,TaySachs,albinism
Autosomaldominant
e.g.,HuntingtonsDisease
Xlinkedrecessive(meaningthisalleleisfoundononlytheX
chromosome:canbeinmalesorfemales)
e.g.,colorblindness,hemophilia
Xlinkeddominant(meaningthisalleleisfoundonX
chromosomes;canbeinmalesorfemales)
e.g.,hypophosphatemia
Ylinked(meaningthealleleisfoundontheYchromosome
andcanonlybeinmales)
Autosomalrecessivetraits

Traitisrareinthepedigree

Traitoftenskipsgenerations
(hiddeninheterozygous
carriers)

Traitaffectsmalesand
femalesequally

Possiblediseasesinclude:
Cysticfibrosis,Sicklecell
anemia,Phenylketonuria
(PKU),TaySachsdisease
Autosomaldominantpedigrees

Traitiscommoninthepedigree
Traitisfoundineverygeneration
Affectedindividualstransmitthetraittoabout1/2oftheir
children(regardlessofsex)
Autosomaldominanttraits

Therearefewautosomal
dominanthuman
diseases(why?),but
someraretraitshavethis
inheritancepattern
Forexample:
achondroplasia(a
sketelaldisordercausing
dwarfism)
Huntingtonsdisease:anexampleofADdisorder
- Half the people in the
Venezuelan village of
Barranquitas are
affected
- A large-scale pedigree
analysis was conducted
including 10,000 people
- Example for one
particular family:
Xlinkedrecessivepedigrees

Traitisrareinpedigree
Traitskipsgenerations
AffectedfathersDONOT
passtotheirsons
Malesaremoreoftenaffected
thanfemales
Femalesarecarriers(passed
frommomtoson)
Hemophilia:anexampleofXlinkedrecessive
disorder
Xlinkedrecessivetraits
ex.HemophiliainEuropeanroyalty
Xlinkedrecessivetraits

ex.Glucose6PhosphateDehydrogenasedeficiency
hemolyticdisordercausesjaundiceininfantsand(oftenfatal)
sensitivitytofavabeansinadults

themostcommonenzymedisorder
worldwide,especiallyinthoseof
Mediterraneanancestry
maygivetheindividualresistanceto
malaria
Xlinkeddominantpedigrees

Traitiscommoninpedigree
AffectedfatherspasstoALLoftheirdaughters
Malesandfemalesareequallylikelytobeaffected
Xlinkeddominantdiseases

Xlinkeddominantdiseasesareextremelyunusual
Often,theyarelethal(beforebirth)inmalesandonlyseenin
females
ex.incontinentiapigmenti(skinlesions)
ex.Xlinkedrickets(bonelesions)
PedigreeAnalysisinreallife

Remember:
dominanttraitsmayberareinapopulation
recessivetraitsmaybecommoninapopulation
allelesmaycomeintothepedigreefrom2sources
mutationhappens
oftentraitsaremorecomplex
affectedbyenvironment&othergenes