MENDELIAN GENETICS 3
SEX LINKED AND SEX-LIMITED INHERITANCE
Genes located on the X or the Y chromosome are said to be sex-linked.
Two types of Sex-linkage
Y Linkage:
Y chromo determines the differentiation of the embryo into maleness
e.g. gonads into testes, spermatogenesis etc
Females are normal in all aspects, but lack a Y chromosome.
Indicates the Y chromosome is not involved in normal development
Very few genetic characteristics transmitted by the Y chromosome.
No problem in identifying them in a pedigree,
ALL males will display the trait,
but no females will.
This type of Y linkage inheritance is referred to as HOLANDRIC inheritance.
Pedigree example
X linkage: Genes located on the X chromosome
Differs from autosomal inheritance because males possess only one X-chromosome.
Recessive traits which are masked in females in the heterozygous state
but
will be exposed in males, who cannot be heterozygous at this loci on the X-chromosome.
Sex-linked RECESSIVE traits appear in males at the same frequency as the allele frequency.
but
Most sex-linked recessives occur in the heterozygous state in females,
thus
the phenotypic frequency of sex-linked traits is very much lower in females
Males transmit their X-chromosome to their daughters
but
their Y-chromosome to their sons,
Thus
all alleles on the father's X-chromosome will be present in his daughters, but none in his sons.
X SEX-LINKED RECESSIVES CANNOT BE TRANSMITTED FROM FATHER TO SON,
BUT ALL DAUGHTERS OF AN AFFECTED FATHER WILL BE AT LEAST CARRIERS.
X sex linked recessive example:
Haemophilia
A condition involving defective clotting of the blood
Prolonged bleeding, usually following injury but sometimes spontaneous internal bleeding, is the essential symptom.
Commonest form, Haemophilia A, usually appears in early childhood or even infancy
due to a deficiency of one of the blood's clotting factors, a protein called anti-haemophiliac globulin, or AHG:
The severity of haemophilia A is very variable, although relatively constant within a family, which suggests that there are a number of different alleles of the haemophilia A gene.
Haemophilia B (sometimes called Christmas disease) involves the deficiency of a different clotting factor:
A mixture of blood from a person with haemophilia A and one with haemophilia B will clot normally, even though each on its own shows very delayed clotting.
queen Victoria pedigree
Transmission of Dominant X linked traits:
X linked HYPOPHOSPHATEMIA
Symptoms:
Low levels of phosphorus in the blood serum
Affected individuals develop rickets which can not be cured via vitamin D administration
Genotype:
Dominant on the X chromosome, therefore if present the recipient shows the trait
Gender Bias:
Occurs in both males and females
Generally more extreme in males
Mode of Inheritance
XR Y male with the disease
Xr Y male without the disease
Xr Xr Female without the disease
XR Xr Female with the disease
XR XR female with the disease
The pattern of inheritance of this allele can be seen in the pedigrees below
Men with the disease have only affected daughters and normal sons
Women heterozygous for the trait will produce affect sons, non affected sons, affected daughters and non affected daughters
Women homozygous for the trait produce only affected offspring.
2. Sex-limited or sex-influenced traits
One which is genetically determined by an allele or alleles located on an autosome,
but which is only expressed in one sex.
Genetically-based variation in secondary sexual characteristics is frequently controlled by autosomal genes.
Variations in beard growth are autosomally controlled,
Only phenotypically expressed in males since females normally lack beards: these variations are therefore sex-limited traits.
sex-influenced trait, "pattern baldness", an uncommon form of baldness involving extensive hair loss usually at about age 25.
Controlled by an autosomal locus but rarely expressed in women.
Occurs as the relevant allele is dominant when it occurs in males,
but is recessive in females.
It is not known what causes the difference in dominance status between the sexes.
INDEPENDENT ASSORTMENT, LINKAGE AND RECOMBINATION
Two or more different loci are said to be linked if they occur on the same chromosome
If the loci are NOT on the same chromosome -
ie are not linked,
each locus will segregate independently (independent assortment).
NON linked loci
albinism (A normal pigmentation, a albinism)
and
Phenyl thiocarbamide, or PTC; (ability to taste PTC is dominant to inability)
The full range of possible genotypes involving these two loci are AATT, AATt, AAtt, AaTT, AaTt, Aatt, aaTT, aaTt, and aatt.
cross for non linked alleles between a
female homozygous for pigmentation, hetero for PTC AATt
and a male heterozygous for both traits AaTt
1. AATt x AaTt
Male gametes
| |
AT
|
At
|
aT
|
at
|
Female
|
AT
|
AATT
|
AATt
|
AaTT
|
AaTt
|
gametes
|
At
|
AATt
|
AAtt
|
AaTt
|
Aatt
|
|
AT
|
AATT
|
AATt
|
AaTT
|
AaTt
|
|
At
|
AATt
|
AAtt
|
AaTt
|
Aatt
|
Offspring genotypes will be 2AATT : 4AATt : 2AAtt : 2AaTT : 4AaTt : 2Aatt
Offspring phenotypes will be 12AT : 4At - ie, 3AT : 1At
Double heterozygotes (this situation is often called a 'dihybrid cross')
2. AaTt x AaTt
Male gametes
| |
AT
|
At
|
aT
|
at
|
Female
|
AT
|
AATT
|
AATt
|
AaTT
|
AaTt
|
gametes
|
At
|
AATt
|
AAtt
|
AATt
|
Aatt
|
|
aT
|
AaTT
|
AaTt
|
aaTT
|
aaTt
|
|
at
|
AaTt
|
AAtt
|
aaTt
|
aatt
|
Offspring genotypes will be 1AATT : 2AATt : 1AAtt : 2AaTT : 4AaTt : 2Aatt : 1aaTT : 2aaTt : 1aatt
Offspring phenotypes will be 9AT : 3At : 3aT : 1at
When loci are linked, i.e occur on the same chromosome, they will not segregate independently: that is, all possible genotypes will NOT be equally likely in the gametes.
___ __
- BbQq x BbQq
----- -------
Male gametes
| |
BQ
|
bq
| | |
Female
|
bQ
|
BbQQ
|
bbQq
| | |
gametes
|
Bq
|
BBQq
|
Bbqq
| | |
| | |
| | |
| | |
| | |
Offspring genotypes will be 0BBQQ : 1BBQq : 0BBqq : 1BbQQ : 0BbQq : 1Bbqq : 0bbQQ: 1bbQq : 0bbqq
Offspring phenotypes will be 2BQ : 1Bq : 1bQ : 0bq
Crossing over:
The closer the loci are to each other on the chromosome, the less likely it is that crossing-over will occur between them.
parental combinations are more likely than recombinants
Frequency of Alleles in the population:
eg Colour blindness Sex linked (X chromosome)
8% of males have the trait,
Thus
8% of the X chromosomes in the population carry the recessive allele.
Therefore 100% - 8% = 92% of X chromosomes in the population carry the dominant allele.
Therefore the probability of a female with two dominant alleles is
0.92 * 0.92 = 0.8464 or 85%
The probability of a female having one dominant and one recessive is
- * 0.08) + (0.08 * 0.92)
= 0.0736 or 7%
The probability of a female having two recessives is
0.08 * 0.08 = 0.006 or 0.6%