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EXPERIMENT 18 PEDIGREE ANALYSIS

FROM PEDIGREE
CHARTS

Structure

18.1 Inlroduction
Objectives
18.2 procedure for Constructing Pedigree Charts
18.3 Autosomal Dominants
18.4 Autosomal Recessives
18.5 Sex Chromosomal Dominants
18.6 Sex-linked Recessive Traits

18.1 INTRODUCTION

In exercise 15 you have studied certain of human traits which follow the
Mendelian concept of dominance-recessive relationship. You are aware that
Mendel followed the inheritance of such traits in pea plant through successive
generations by controlled crosses.' Also, such crosses led to the deduction of
principles of segregation and independenl assortment. These principles are
applicable to all plants and animals including human beings. But the type of
1
crossing experiments done with plants and animals, cannot be performed on
humans. Therefore, other methods are used to study the humari jnheritance
patterns. One method that is extensively used by human geneticists and genetic
counsellors is the conslruction and analysis of pedigree charts. The pedigree
charts consist of a set of symbols which convey the details regarding the'
transmission of a trait over a number of successive generations. It is possible,
after a.carefu1 study of pedigree chart to conclude whether a trait is dominant
or recessive and whether it is an aulosomal trait or a sex linked one. In this
exercise we shall learn to draw pedigree charts and analyse them meaningfully.
Make sure that your are familiar with the concepts of autosomal and sex
chromosomal inheritance from your studies on LSE-03 course.
/

Objectives

From this experiment; you should learn:

to explain various symbols that are commonly used in pedigree charts
to draw a pedigree chart based on the data available or given
to analyse and interpret pedigree char1 and assign the trait to autosome or
sex chromosome and say whether the concerned allele is dominant or
recessive.

18.2 PROCEDURE FOR CONSTRUCTING PEDIGREE

CHARTS

Before we begin constructing or analysing the pedigree charts it is necessary to

1,aborntory Course-I become familiar with diffcrcnt symbols that are commonly used in pedigree
charts. Table 18.1 provides you thc symbols used and their meanings. We shall
begin with the construction or a simple pedigrcc chart and then start analysing
the more complcx ones.

Table 18.1: Symbols used in Pedigree Charts

Normal fcmale

Normal male

Indicates marriage

Indicates consanguinous mating or maling between close

rclatives.

Nonnal parcnts wilh 3 nor~nalchildren, 2 daughlers and

one son.

Roman numcrals denote generation numbers and arabic

numcrals, the ordcr in which the children arc born.

Only a single parent is shown as h e olhcr parent is

normal and is of no significance in pcdigree analysis.

7. Fraternal twins or lwins arising from two dirkrcnt zygolcs

(dizygolic).

Identical twins or lwins arising from a single zygolc

~monozygotic).

Scx unknown.

Number of children for each scx

Shaded circle or square indicatcs a c c t c d daughtcr or son.

An arrow bclow Lhe affected individuals indicatcs Lhat the

analysis bcgins from [hat individual. Thc individual is an
index case. The dfccled iildividual is lhus a proband or
propsitus.

Aulosomal hclerozygous recessive.

Sex linked carricr individual.

Deceased individual.

Aborted foctus or a stillborn child.

Hurnans fall into two categories dcpencling on their ability Lo tnstc n chcrnical
the phcnylllliocarbamide (PTC). Thc tasters taste this chemical bittcr and the
non-tastcrs do not taste the chcmical at all. Thc allclc T dctermillcs the ability
to tastc PTC and people who are homozygous recessive to thc allele (tt) are
non-taslcrs. Wc have the following data on tastc blindness horn a family,
 The female ,parent is a non-taster and Lhe couple had five children, t h r c ~ Pedigree Analysis from
daughters and lwo sons, of whom a son and a daughter are non-tasters. One Pedigree Charts
of the Laster daughters is married to a non-tastcr man. This couple had eigh~
childrcn, five sons and thrce daughtcrs, of whom two sons and a daughter
arc non-tasters.

Bascd on Lhe dnla provided, we may construct a pcdigrec chart to show the
i~ficl-itanccpaltcm of non-lsstcr allcle in thc family.

Fig. 18.1

The pedigree (Fig. 18.1) shows that Lhc fcmalc parcnl is a non-tastcr. Similarly
11-1 and 11-6 individuals are non-taslcrs; so also 111-3, 111-7 and 111-8
individuals. It is possible to dcduce from thc pcdigrcc thal Lhe trait is
dctemincd by an autoso~nxlallcle. Thc ~ncthodof deducing is discussed bclow.
Bricfly il could bc said hcrc thal i f thc allcle wcsc lo bc a scx linkcd trait, all
lhc malcs of h e second gcncration would havc inllcrilcd it. You have learnt
Sroln unil 4 or Gcnctics coursc that scx linkcd charactcrs arc gcncrally
transfcrrcd fronr molllcr to sons and from fathcr Lo daughlcrs, a phcnomcnon
known as criss-cross illhcrilance. From lllc pcdigrcc charl il is possiblc to
dcducc whclher thc trail is a dominant onc or rcccssive. Assunling ~ h Lraitc is a
donlinanl one and lhc f:~Lhcris homozygous for il (TT),thcn Llic 111oi.hcr will bc
l~omozygousrcccssivc (tt). All Ulc childrcn of Uiis couple, Lhcn would
ncccssarily be Laslcrs and hclcrozygous (TI). Howcvcr, Lllis is 1101 tllc casc hcrc.
Assuming the father is hclcrozygous dominant, Lhcn half Ihcir cllildrcn would
be non-taslers and Ulc olhcr half tastcrs. Morc or lcss thus nppcars lo bc thc
case in thc pcdigrec citcd. Thc 11-4 fcn~alc,a tastcr is morricd Lo J non-taslcr.
Assuming shc is also hclcrozygous dominant, tlicn hal1 of thc c! ~ldrcnwould bc
non-taslcrs and thc othcr half tastcrs. Thc data suggcsts that Lllis is so in thc 111
, generation. So could lhc tastcr allclc be dominant?

Assuming lhc taster allcle to be a rcccssivc onc, and the lcmalc or gcncralion is
hetcrogyzous for non-tastcr ~rait,then again rcsulls similar to thc onc shown in
thc pedigrec chart would bc obtained.. Thc pcdigrcc chart is Ihus incomplclc in
Lhc scnsc that il docs not hclp us to dccide whclhcr thc conccrncd allclc i s
dominanl or rcccssivc. Essclllially ~ h cchart has to bc cxpandcd by collecting
more data on Lhe family. Lct us say Lhat wc havc ;\dditional data. The 111-8
fcmalc, a non-tastcr is mauicd 10 a tastcr maIc and has four cllildrcn all oP
whom arc tnstcrs. Lct us now rcdraw tllc pcdigrcc char1 wilh thc additional
information (Fig. 18.2).
 1 2 3 4
Fig. 18.2

Now, the 111-8 and 111-9 individuals arc marricd and havc four tastcr children.
This part of pcdigrce chart hclps us to dclcnllinc beyond any doubt the
dominance or rccessivcncss 01thc allclc. Thc fact lhat all the four childrcn born
to 111-8 and 111-9 parcnts arc tasters and that only onc of the parents is a Laster,
clcal-ly tells us Lllat Lhc falhcr is homozygous dominanl (TT)and Lhe ~nolheris
rcccssivc (Lt) (Fig. 18.3).

tt X Tr
(non-taster) 1 (taster)

Tt TL Tt Tt
(tastcr) (taslcr) (tastcr) (tastcr)
Fig. 18.3

Therefore, Lhe allele in qucslion is a dominarlt allele. Esscnliidly PTC tastcr trait
is an autoson~aldominant trait.

Ccrtain gcneral patlcins can bc 10Llowcd to idcnlify wllclhcr a trait is autoso~nal

or sex chromosomal and whcthcr il is dominant or a rcccssivc one. Lct us
catcgorisc these patterns.

18.3 AUTOSOMAL DOMINANTS

a) Autosoinal dominant trails makc Ihcir appearance invariably in all

generations.' In othcrwords, they do not skip generations.

b) An individual carrying the gcne for the alfccted trait (hetcrozygous) married
to a normal individual generally produccs normal offspring to affcctcd ones
in the ratio of 1:1.
C) Thcre is no discrimination.bctween scxes and thc trait is distributed cqually
in both the sexes.
Thc pcdigrce in Fig. 18.4 shows thc gcneral pattern of inheritance of an
autosoma1 dominant trait. Study the pedigrce carefully and makc sure that the
pattcln of autosomal dominant inheritance conforms to thc statements we madc
abovc.
 I Pedigree AnJgsls from
Pedigree Churts

Fig. 18.3.

Brachydactyly, Hurtlington's disease, ability to taste phenylthiocarbarnide and

polydaclyly arc somc of thc autosomd dominant traits in humans.

115.4 AUTOSOMAL RECESSIVES

3) Unlikc the autosomal dominant traits, thc autosomal rccessivc ones do not
make thcir appearance in cvcry gencration. In othcr words, they may skip
certain generations and appcar only in ccrtain olhcrs.

b) Like autosomd dominants, the distribution is equal bctwccn Ihe two sexes.

c) They are more commonly found among childrcn born to consanguinous

couples, that is couplcs who wcrc lirsl cousins bcl'orc ~narriagcor otherwise
closcly rclatcd.

d) If boll1 the parcrlts arc attcclcd, d l Ihc childrcn born to thcm will also be
4 artcctcd.

e) The parents of the affected childrcn may bc normal.

r) Thc affectcd child born to a normal parents essentially suggcsts that the
pnrcnts arc heterozygous and are carriers of the allclc for Lhc trait.

g) If bolh the parcnts are heterozygous, thcn thc chances arc that
approximately 50% of tlie childrcn born to Lhem would inherit the recessive
trail.

Thc pedigrcc givcn in Fig. 18.5 is an example of Lhe inhcritancc pattcrn of

albinism in humans. Albinism is a rare autosomal reccssive trait and rcfers to a
condi!ion in which a pcrsol-l cannot synthesist the pigment melanin. Study h e
pcdigrec carclirlly and vsrify hat tile ulhcritmcc 01albinism follows the pattcm
that is chataclcristic of an autosomal reccssivc Lrait.
 Fig. 18.5

An analysis of the pcdigrec in Fig. 18.5 shows that 111-2 individual is an

albino, although both hcr parcnts are nonnal. Essentially they should be
hclerozyous and the daughter rcccivcs the two recessive alleles. Also
individuals IV 2, 4 and 6 are also albinos, suggesling that Lhcir Iathcr is also
heterazygous. Since both IV 1 and 2 are albinos their daughter is also an
albino. The possible genotypes of the above pedigree can be written as follows
(Fig. 18.6).

I
,
AA x Aa
1 2 , ,A?jA;,
I1 AA? AA? Aa x Aa AA? AA? The question mark suggests
1 2 3 1 4 5 G that the genotypcs of
An x aa
I11 1 2 individuals could be cilher
AA or Aa.
1 I 1

v aa
1
Fig. 18.6

18.6 SEX CHROMOSOMAL DOMINANTS

a) As in thc case of autosomnl dominants, in thc inheritance of sex linked

dominants also the gcncraiions arc not skippcd.

b) Males always ulhcrit thc trait Irom thcir mother. I

c) Fcmalcs may rcceivc tlic dominant allelc either from thcir mother or Iron1 I

thcir falhcr.

d) IT Lhc fcmalc is aTfcctcd, Lhcn approximately half of her-sons and half of

hcr daugl~tcrs are arfcctcd.

c) IT lhc male is alfccted lhcn all his dnughtcrs will be affcclcd but none or
his sons will be affcctcd.
 Scx linked dominant traits arc vcry rare. A sex linked dominant trait is oral- Pedigree Analysis from
I'i~cial-digitalsyndromc which rcsults in cleft tongue, absencc of. tcclh and Pedigree Charts
mcnlal rclardation. Othcr scx linkcd dominat allclcs responsible for ccrtain
cliscascs include thc allcle for Albriig'tlt's hereditary ostcodystrophy causing
suizurcs, stunlcd growth and nlcntal rclardalion, Goltz's syndrome whosc
symptoms arc meiltal retardation, small eyes and flexed digits and incontincntia
pigmcnli which causcs thc non-relcnlion or mclanin in mclanoblasts. Fig. 18.7
shouls a pcdigrce ior ollc such sex-linked dominant trait.

Fig. 18.7

You nlay obscrvc in thc R g 18.7 that the trait appears in all gcncrations; and
thc trail always passcs fiVomthc f~~11cr to thc daughtcrs and not to the sons
(Notc that 111-3 illalc has passcd the trait to all his daughters but Lhc two sons
arc normal).

18.6 SEX-LINKED RECESSIVE TRAITS

a) Since males have only onc X-chromosome and reccivc the samc from thcir
molhcr, Ihey are thc ones most aifcctcd by scx linkcd rcccssivc allclcs.

h) Gencr:~lly,the fccmalcs arc caniers of thc rcccssivc allcle and Ulus

l~ctelozygousin gcnulypls.

c) Thc females arc kn0vv.n to bc hctcrozygous bccausc of affcclcd brothers,

iathcrs or maternal uncles.

d) Malcs reccivc the X-linkcd rct;cssive trait from thc thcir molhcr.

c) Females cxpress thc trail only whcn lhcy have a hornozygous rcccssive
genotypc and Ulc allclcs arc rcccivcd rrom carricr mothers and affcctcd
fathers.
I

f) All the sons of an affcctcd fcmalc arc aficctcd and 50% of thc daughtcrs
arc carriers.

g) Ncarly 50% or the sons of thc carricr fcmalc would bc aifectcd.

Scvcrnl scx linkcd rcccssive traits arc known in humans and haemopl~liais the
most fanous case of scx linkcd recccsi\lc inhcritancc. Colour blindncss, the
~ a b o l - a i o Course-I
r~ inability to distinguish rcd and grccn colours is another onc. Many dcficicncics.
relating lo cnzymes such as G-6-PD deiicicncy (glucose 6 phosphalc
dehydrogenasc deficiency) arc also sex Linkcd. Thc pattcln of iliheritance of a
sex linked recessive allele is shown in thc Fig. 18.8

Ill

Fig 18.8

111 the casc of scx linked rcccssive iul~crilance,the number 01males afrectcd are
always more than femalcs. This is cssentidly due to the fact Lhat the rnalcs
rcccive only onc X chromoso~neand that is received from the molhcr. You can
observe from Fig. 18.8 Lhnl 111-3, a no~malfemale manied LO 111-4, an afIccLcd
male @vcs birlh to 3 children, 2 daughters and one son. Sincc lhc son is
aIfccLcd, it is obvious thal the mothcr is Lhc canicr of the recessive allcle and
has passcd Ihc trait to Mm.

Shnilarly, 111-8, 1V-7 and IV-14 arc hctcrozygo~is~nolhcrswho haw passed Lhc
trait to thcir son.

We have illus Pdr discussing UCI analysis 01 pcdi~rcecharts and assign the trdts
to nutosomcs or sex chromosome and to idcnLily Lllcnl as dominant Or
recessive ones. You may now work on the following problcms LU ~ c s lyour
understanding oJ pcdigrcc charts.

1. Analyse t l ~ efollowing pedigrce and answer the questions as directcd.

 Pedigree Analysis from
Pedigree Charb

Fig. 18.10

I a) Is the trait an autosomal or a sex chromosomal one?

I S

i b) Is the gene that causcs the trait a dominant or a recessive one?

1
I

c) What could be the genotypes of 1-1, 1-2, 11-1, 11-6, 11-7, 111-5 and 111-7
11
individuals, assuming the dominant allele is S and recessive allele is s.

2. Below is given the pedigree of a family, certain individuals of which are

affected by aninherited metabolic disorder alkaptonuria. The disease is
caused by a defect in the metabolism of the amino acid: phenylalanine,
Answer the questions given below after a careful analysis of the p c d i g ~ e .

Fig. 18.11

1) Does the above pedigree suggest an autosomal or sex chromosomal

inheritance?

2) Does the inheritance pattern suggest the involvcmcnt of a domi~antallele

or a recessive allele?

3) How would you explain the rnamage between 111-3 and a IV-I individuals?

4) Assuming the dominant and rccessive alleles are designated as A and a.

what are the gennt\:pe\ J-2, !I-3, 11-4, 111-3 and IV-1 individuals?
;,if