Linked Genes, Sex Linkage and Pedigrees Chapter 15 Pages333 - 354.
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Transcript of Linked Genes, Sex Linkage and Pedigrees Chapter 15 Pages333 - 354.
Linked Genes 1Genes on the same chromosome are said to be linked. They are inherited together as a unit and do not undergo independent assortment.
Linkage can alter expected genotype and phenotype ratios in the offspring.
In this example, only two types of gamete are produced instead ofthe expected four kinds if the geneswere assorted independently.
Genes A and B control different traits and are on the same chromosome
aBaBGametes AbAb
Meiosis
One homologous pair of chromosomes
Oocyte
Linked Genes 2
Genes located on the same chromosome are said to be linked (e.g. genes A and B).
Linked genes tend to be inherited together.
Linkage results in fewer genetic combinations of alleles in offspring (compared to genes on separate chromosomes).
In describing linkage, the appropriate notation shows a horizontal line separating linkage groups.
Chromosome pair before replication
Chromosomes after replication
Parent 2 (2N)Parent 1 (2N)
LinkedLinked
ABab
abab
Line indicates linkage
Two genes are linked when they are on the same chromosome
Linked Genes 3
The inheritance patterns involving linked genes do not follow expected Mendelian ratios.
In this example of linked genes, only two kinds of genotype combinations occur in the offspring.
Without linkage, the same parents would provide four possible genotypes: AaBb, Aabb, aaBb, aabb.
Chromosomes after replication
X
Possible offspringOnly two genotype
combinations occur
AaBb AaBb aabb aabb
Meiosis
Only one
gamete from
each replicated
chromosome is
shown
Gametes (N)
RecombinationRecombination refers to the exchange of alleles between homologous chromosomes as a result of crossing over between linked genes.
Recombination results in new combinations of parental characteristics in the offspring.These offspring are called recombinants.
Recombination between allelesof parental linkage groups isindicated by the appearance of recombinants in the offspring,although not in the proportionsthat would be expected withindependent assortment.
Recombinant
offspring
Non-recombinant
offspring
Off
spri
ng
aaBbAabbaabbAaBb
Gam
etes
(N
)Meiosis
AB Ab aB ab ab ab ab ab
Before replication
AB
ab
ab
ab
Parent 2 (2N)Parent 1 (2N)
Linked genes
Crossing over has occurred
After replicationX
Autosomal & Sex-Linked GenesGenes on one or other of the sex chromosomes produce inheritance patterns different from that shown by autosomes:
Autosomal Genes
1. All individuals carry two alleles of each gene
2. Dominance operates in both males and females
3. Reciprocal crosses produce the same results
4. Alleles passed equally to male and female offspring
Sex-Linked Genes
1. Males carry only one allele
of each gene (hemizygous)
2. Dominance operates in females only.
3. Reciprocal crosses produce different results.
4. ‘Criss-cross’ inheritance pattern: father to daughter to grandson, etc
Sex Linkage
Sex linkage refers to the phenotypic expression of an allele that is dependent on the sex of theindividual and is directly tied to the sex chromosomes.
Most sex linked genes are present on the X chromosome (X-linkage) and have no corresponding allele on the smaller male chromosome.
In some cases, a phenotypic trait is determined by an allele on the Y chromosome. Because the Y chromosome is small and does not contain many genes, few traits are Y-linked and Y-linked diseases are rare.
Note the size differences between the X and Y chromosomes. The Y lacks alleles for many of the genes present on the X.
X
Y
Affected son
X Y
Sex LinkageSex-linked traits show a distinct pattern of inheritance.
Fathers pass sex-linked alleles to all their daughters but not to their sons.
Mothers can pass sex-linked alleles to both sons and daughters.
In females, sex-linked recessive traits will be expressed only in the homozygous condition.
In contrast, any male receiving the recessive allele from his mother will express the trait.
Carrier daught
er
XX
Unaffected
daughter
XX
Unaffected son
YX
Carrier
mother
X XX Y
Unaffected
father
Pedigree AnalysisPedigree analysis is a way of illustrating inheritance patterns. It is a good way to follow the inheritance of genetic disorders through generations.
Sex
unknown
Generati
ons
I, II, III
Children (in birth
order)
1, 2, 3
Non-
identical
twins
Died in
infancy
Carrier
(heterozyg
ote)
Affected male
Affected
female
Normal male
Normal female
Identic
al
twins
Symbols are used to represent males, females etc. For traits of interest, symbols can be shaded to indicate individuals carrying the trait.
Individuals are designated by their generation number and then their order number in that generation.
Sex Linked Recessive InheritanceFor a recessive trait controlled by a gene on the X chromosome, the features of inheritance can be illustrated with the standard symbols used on pedigree charts. Note that:
More males than females express the trait.
Carrier females do not show the trait but pass it to sons.
All daughters of affected males will at least be carriers of the trait.
Affected maleUnaffected female
Carrier
Famously, Queen Victoria was a carrier of the allele for hemophilia, passing it to one of her sons and, through her daughters, to the royal families of Prussia, Russia, and Spain.
Sex Linked Dominant Inheritance
Sex-linked dominant inheritance is rarer because all daughters of affected males will be affected (the heterozygous condition is not a carrier).
Sex-linked dominant traits are never passed from father to son.
Affected females produce 50% normal and 50% affected offspring.
Unaffected female
Affected male
Some X-linked dominant conditions, such as
Aicardi syndrome, are lethal to boys. They are
usually seen only in girls but may be seen in
males with Klinefelter syndrome (XXY)
Sex Linkage in HumansA rare form of rickets in humans is a sex-linked dominant trait. It is determined by a dominant allele of a gene on the X chromosome.
This condition is not treatable with vitamin D therapy.
A typical inheritance pattern is shown. XR indicates affected by rickets.
Nor
mal
wom
an
Affect
ed
maleParents X
Genetic Counseling
In the example of the sex-linked dominant form of rickets, the ratios of affected children can be determined if the phenotype and genotype of each parent is known.
In this case, the prospective parents would be advised that there is a 50% chance of having an affected child. Only girls would be at risk.
Possible
fertilizatio
ns
Children
Affect
ed
femal
e
Nor
mal
male
Affect
ed
femal
e
Normal
male
XXRXY XYXXR
Gametes YXRXX
XRYXX
These are inherited disorders caused by dominant alleles on autosomes. Dominant conditions are evident both in heterozygotes and in homozygous dominant individuals. Examples include:
Huntington disease
Autosomal Dominant Disorders
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.
Autosomal Recessive Disorders
(Pho
to: U
K C
ystic
Fib
rosi
s G
ene
The
rapy
Con
sort
ium
)
Inherited disorders caused by recessive alleles on autosomes. Recessive conditions are evident only in homozygous recessive genotypes. Eg. Cystic fibrosis.
The pedigree for albinism (lack of pigment in the hair, skin and eyes) is inherited as an autosomal recessive trait.
The trait is not sex linked and is shown by both males and females. The affected female in the third generation has phenotypically normal parents.
All generation II offspringare carriers for the albinoallele.
III-2 is an albino girl whosepaternal grandmother andmaternal grandfather arealso albinos.
All her other relatives are phenotypically normal.
• 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.
Hemophilia is an X-linked disorder in which blood clotting time is prolonged.
Women who are heterozygotes are carriers for the recessive allele but do not have hemophilia. They can pass the allele to their sons (XY) who will express the recessive allele and have hemophilia.
In the first generation, the femaleof the affected family is a carrierfor the hemophilia allele.
Two of the offspring of the affectedfamily also carry the allele; the maleis affected and the female is a carrier.
Offspring of the female carrier andan unaffected male can be unaffected,carrier females, or affected males.
Inheritance of X-LinkedRecessive Traits
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.
In this rare pattern of inheritance, all the daughters of affected males will be affected and more females than males will show the trait.
An affected male must always have an affected mother.
The inheritance of a rareform of rickets follows thisinheritance pattern.
The male I-2 is affected and allhis daughters II-2, II-3, and II-4are affected.
The affected female II-4 canproduce affected offspring ofboth sexes (III-2, III-3).
Inheritance of X-LinkedDominant Traits
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
Y-linkage
• The Y chromosome has fewer genes and most are involved in male sex
determination and fertility.
• So there are fewer Y-linked genetic disorders.
• Y-linked conditions:
- Hairy ears
- Azoospermia – almost
nil sperm
Is the condition observed in each generation of a family in which it occurs?
Is the condition mainly in males?
If daughters have the condition does their father also have it?
Do males with the condition who mate with a normal female have all daughters, but no sons with the condition?
Do only males have condition, passing it from father to son?
NO YES
ON
NO
YESAutosomalrecessive
Sex-linkedrecessive
NO
YESAutosomaldominant
Sex-linkeddominant
YES
Y linkage
Types of variation• Genetic traits influenced by a single gene usually only have
two or three possible phenotypes.
(EG. Positive or negative blood factor, right or left handed, ear
lobe shape, dimpled chin, hand clasp)
• The population is said to show discontinuous variation for the
trait.
• Data would look like this graph
no in-between variations
just one or the other. 20
0.2
0.4
0.6
0.8
1
1.2 Rh factor
% of popu-lation
• Discontinuous variation can be influenced by more than one
gene.
• For example in budgerigars feather colour is influenced by
three genes that produce seven colours.
• Each colour is distinguishable from the others so they are still
discontinuously variable.
2 3 4 5 6 70
5
10
15
20
25
30
35Feather colour in Budgerigars
% of popula-tion