Sex linkage
and
Pedigrees
Sex determination in mammals
 In humans and some other organisms, X and Y
chromosomes determine the sex of an individual.
 This is because they carry certain genes that are critical
in sex determination, such as the SRY gene on the
mammalian Y chromosome, which controls testis
formation.
 Individuals with two similar sex chromosomes are the
homogametic sex.
(i.e. women XX)
 Individuals with different sex chromosomes are the
heterogametic sex.
(i.e. men XY)
 During the growth and development of females’ cells,
one X chromosome is inactivated in each body cell. The
inactivated X chromosome is visible in a female’s cells
as a Barr body.
Sex determination in other organisms
WZ Chromosome System
 Males are homogametic (ZZ) and females are heterogametic (ZW).
 Birds and strawberries are examples of the W/Z determination.
XO Chromosome System
 Only one sex chromosome.
 Females are XX but males are XO, where the O refers to the absence of a matching
sex chromosome.
 In the XO chromosome system diploid number is therefore even in females and odd
in males.
Sex Determination by haplodiploidy
 Males develop from unfertilised eggs and are therefore haploid.
 Females develop from fertilised eggs and are diploid. Examples include wasps and
bees.
Sex Determination by environmental factors
 Environmental sex determination may depend on:
 temperature (e.g. turtles, crocodiles)
 day length (shrimp)
 richness and availability of food resources (e.g. nematodes).
X linked inheritance
 Males receive their X chromosome from their
mother – so they inherit all X-linked traits from
their mothers. The alleles on this chromosome
will determine the phenotype of X-linked traits
regardless of whether the trait is dominant or
recessive in heterozygous females.
 All females inherit an X chromosome from each
parent. The random nature of X chromosome
inactivation means that heterozygous females
express different alleles in different cells.
X linked inheritance
 X-linked Recessive
disorders
 Show a pattern of
transmission of the mutant
phenotype from the female
parent to male offspring.
 Only females may be
carriers of an X-linked
recessive trait.
 Examples of X-linked
recessive disorders include
haemophilia A, haemophilia
C and red-green colour
blindness.
X linked inheritance
 X-linked Dominant
disorders
 Show a pattern of
transmission of the mutant
phenotype from an affected
male parent to all female
offspring, and from an
affected heterozygous
female parent to 50% of all
offspring.
 Examples of X-linked
dominant disorders include
Vitamin D resistant rickets
and fragile X syndromes
Reciprocal Crosses
 X linkage is often determined by carrying out a reciprocal cross.
 A reciprocal cross is one of a pair of matings in which two opposite sexes
are coupled with each of two different genotypes and mated in opposite
combinations.
 For example, a female of a certain genotype A is first crossed with a male of
genotype B. Then, in the reciprocal cross, a female of genotype B is
crossed with a male of genotype A.
 If the gene is autosomal it will not matter which parent has which
phenotype; all of the offspring will show the dominant phenotype we see in
F1 for any monohybrid cross.
 If it is X-linked, the offspring in F1 or F2 will be different from that expected
in a cross involving autosomal genes.
Example of a reciprocal cross
 Gene which determines eye colour in Drosophila is X-linked. Wild type flies
have red eyes.
 XR – and Xr – white.
 Using purebreeding parental stocks:
 Cross 1:





Red eyed female
X
white eyed male
XRXR
X
XrY
Gametes all XR
Gametes ½ Xr & ½ Y
All female offspring XRXr – red eyed
All male offspring XRY – red eyed
 Cross 2:





White eyed female
X
red eyed male
r
r
XX
X
XRY
Gametes all XR
Gametes ½ Xr & ½ Y
All female offspring XRXr – red eyed
All male offspring XrY – white eyed
 First cross tells us that red is dominant phenotype
 Second cross results are not consistent with autosomal inheritance,
indicating X-linkage.
Y linked inheritance
 There are far fewer Y-linked than X-linked
genetic disorders
 This is not surprising given that the Y
chromosome is smaller and has many
less genes than the X chromosome.
 Y-linked inheritance shows a pattern of
transmission of the mutant phenotype
from father to son, and it is never
observed in females.
 An example of a Y linked phenotypic trait
is hairy ears.
Sex limited inheritance
 Y-linked inheritance is often confused with sexlimited inheritance.
 Sex-limited traits can only occur in one sex
because the feature affected is unique to that
sex.
 For example, premature baldness is an
autosomal dominant trait, but presumably as a
result of female sex hormones, the condition is
rarely expressed in the female, and then usually
only after menopause.
X-inactivation
 During the growth and development of females’ cells,
one X chromosome is inactivated in each body cell.
 The inactivated X chromosome is visible in a female’s
cells as a Barr body.
 Which of the two X chromosomes becomes inactive in a
cell is a matter of chance, therefore heterozygous
females express different alleles in different cells.
 This is generally not noticeable in the phenotype – for
example a woman heterozygous for the recessive
condition haemophilia A will produce sufficient clotting
factor VIII.
 Tortoise shell cats are an example where X inactivation
is visible in the phenotype as one of the genes which
controls coat colour is sex-linked.
X-inactivation




One of the genes that controls coat colour in cats is sex-linked.
It has alternative alleles Xo (orange) and Xb (black)
Patches of cells in which the Xo are inactivated will produce dark fur.
Patches of cells in which the Xb is inactivated will produce orange fur.
Barr body
Pedigree Analysis
 Is the technique of looking through a family tree (of humans or other
organisms) for the occurrence of a particular characteristic in one
family over a number of generations.
 Can be used to determine the likely mode of inheritance:




Autosomal dominant
Autosomal recessive
X-linked dominant
X-linked recessive
 When looking at pedigrees, incomplete penetrance is occasionally
observed.
 Incomplete penetrance describes the situation where a proportion of a
population with a particular genotype does not show the expected
phenotype.
 Complete penetrance of a phenotype means that all individuals with a
particular genotype will show the affected phenotype.
Symbols used in drawing pedigrees
Autosomal Dominant Pattern
 An idealised pattern of inheritance of an autosomal dominant trait includes
the following features:
 both males and females can be affected
 all affected individuals have at least one affected parent
 transmission can be from fathers to daughters and sons, or from mothers to
daughters and sons
 once the trait disappears from a branch of the pedigree, it does not reappear
 in a large sample, approximately equal numbers of each sex will be affected.
Examples include:
 Huntington disease
 Achondroplasia (a form of
dwarfism)
 Familial form of Alzheimer
disease
 Defective enamel of the
teeth
 Neurofibromatosis (the
‘Elephant man’ disease)
Autosomal Recessive Pattern
 An idealised pattern of inheritance of an autosomal recessive trait
includes the following features:




both males and females can be affected
two unaffected parents can have an affected child
all the children of two persons with the condition must also show the condition
the trait may disappear from a branch of the pedigree, but reappear in later
generations
 over a large number of pedigrees, there are approximately equal numbers of
affected females and males.
Examples include:






Albinism
Cystic fibrosis
Thalassaemia
Tay-Sachs disease
Phenylketonuria
Red hair colour
X linked Dominant Pattern
 An idealised pattern of inheritance of an X-linked dominant trait includes the
following features:





a male with the trait passes it on to all his daughters and none of his sons
a female with the trait may pass it on to both her daughters and her sons
every affected person has at least one parent with the trait
if the trait disappears from a branch of the pedigree, it does not reappear
over a large number of pedigrees, there are more affected females than males
Examples include:
 Vitamin D resistant rickets
 Incontinentia pigmenti, a
rare disorder that results in
the death of affected males
before birth
X linked Recessive Pattern
 An idealised pattern of inheritance of an X-linked recessive trait includes the
following features:
 all the sons of a female with the trait are affected
 all the daughters of a male with the trait will be carriers of the trait and will not
show the trait; the trait can appear in their sons
 none of the sons of a male with the trait and an unaffected female will show the
trait, unless the mother is a carrier
 all children of two individuals with the trait will also show the trait
 in a large sample, more males than females show the trait.
Examples include:
 Ichthyosis, an inherited skin disorder
 One form of red–green colour-blindness
 One form of severe combined
immunodeficiency disease
 Haemophilia
 Fragile X syndrome
 Duchenne muscular dystrophy
Is the condition observed in each generation of a family in which it occurs?
NO
YES
If daughters have the
condition does their
father also have it?
NO
Autosomal
recessive
Do males with the
condition who mate
with a normal female
have all daughters,
but no sons with the
condition?
ON
Is the condition
mainly in males?
Do only males have
condition, passing it
from father to son?
NO
YES
Sex-linked
recessive
Autosomal
dominant
YES
YES
Sex-linked
dominant
Y linkage