BZ1001 Mendelian Genetics 2
INHERITANCE OF MENDELIAN TRAITS.
As a result of meiosis and fertilisation
offspring receive one set of chromosomes from parents:
half from the father and half from the mother.
If parent is heterozygous,
offspring can only inherit one of the two alternative alleles
the chances of inheriting each of the alternatives are equal
Mendel's 'segregation' law
Simplest patterns of inheritance are shown by single autosomal gene
(ie by a single gene not located on the sex chromosome).
An example of a recessive trait: The inheritance of albinism.
Albinism
1 in 38000 whites and about 1 in 22000 blacks.
Albinos synthesise little or no melanin, the pigment commonly found in skin, hair, and eyes.
There are several forms of albinism, but the commonest results from the lack of a particular enzyme (tyrosinase) which is needed to synthesise melanin.
The trait is recessive;
that is, heterozygotes are not albinos.
The allele for albinism as a,
normal pigmentation as A.
An albino genotype aa;
Normal has a genotype AA. or Aa
All gametes from albino will carry the a allele,
Gametes from normal will carry only the A allele if homozygote
but
A or a if heterozygote
People heterozygote for the trait are carriers of the recessive allele for albinism.
Punnet squares
Monohybrid cross between two individuals who are homozygote dominant.
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Homozygous gametes
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Homozygous gametes
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A
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A
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A
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AA('normal')
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AA('normal')
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A
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AA('normal')
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AA('normal')
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AA = 4 Genotypically homozygous, phenotypically normal pigmentation
Aa=0 Genotypically heterozygous, phenotypically normal pigmentation
aa=0 Genotypically homozygous, phenotypically albino
Monohybrid cross between two individuals who are carriers for the albino trait.
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Heterozygous 'normal' parents gametes
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Heterozygous gametes
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A
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a
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A
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AA('normal')
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Aa (carrier)
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a
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aA (carrier)
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aa (Albino)
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AA = 1 Genotypically homozygous, phenotypically normal pigmentation
Aa=2 Genotypically heterozygous, phenotypically normal pigmentation
aa=1 Genotypically homozygous, phenotypically albino
Monohybrid cross between two individuals, one who is an albino and one who is a carrier.
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Homozygous albino parents gametes
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Heterozygous gametes
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a
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a
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A
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Aa (carrier)
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Aa (carrier)
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a
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aA (Albino)
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aa (Albino)
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AA = 0 Genotypically homozygous, phenotypically normal pigmentation
Aa=2 Genotypically heterozygous, phenotypically normal pigmentation
aa=2 Genotypically homozygous, phenotypically albino
Albinism is a deleterious trait: that is,
disadvantageous to the individual who possesses it.
Strongly deleterious Mendelian traits are usually recessive
WHY?
Allele for albinism has a frequency of about 1 in 195 in US whites
Albino phenotype is very much lower i.e 1 in 38000 in whites
Autosomal dominant trait: Huntington's disorder.
Symptoms:
Can begin in early childhood, but most often the symptoms appear after age 35
Changed personality, diminished facial expression, slurred speech, stiff limbs
35-50 years a progressive deterioration of mental and motor performance (loss of brain cells -death
Frequency of occurrence
Relatively rare; 1/16000 births
certain regions where it is common e.g. north eastern America and Tasmania (1/5500)
Genotype
Usually heterozygous (Hh)
Unlikely to be homozygous (HH)
Gender Bias
Theoretically both genders are equally likely to have the condition,
however,
more likely to occur in men.
NB not normally the case with autosomal dominant disorders.
PUNNET SQUARE
Monohybrid cross for Huntington's disorder between a heterozygote and a homozygote recessive.
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Heterozygous parents gametes
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Homozygous parents gametes
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H
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h
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h
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Hh (sufferer)
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hh (clear)
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h
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Hh (sufferer)
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hh (clear)
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HH = 0 Genotypically homozygous, phenotypically sufferer
Hh=2 Genotypically heterozygous, phenotypically sufferer
hh=2 Genotypically homozygous, phenotypically clear
Determination of risk:
Children of an affected parent have a 50% chance of getting the disease
PKU: An Autosomal recessive and possible incomplete dominance
Phenylketonuria
Symptoms
Cannot synthesise the enzyme phenylalanine hydroxylase
Phenylalanine builds up to excessive levels in the liver and spreads through the blood stream, affecting the brain in particular
Brain weight is reduced: Myelin (the sheath around the nerve fibres, dendrites (fine processes linking nerve fibres and synapses (junction of the nerve fibres are all deficient.
Untreated people usually have an IQ of less than 20 and have abnormal reflexes and posture
Commonness
Relatively rare; 1 in 11000- 17000 births (1 in every 5000 for Scots and Irish)
Genotype
Homozygous recessive (pp)
Gender bias
None
Mode of inheritance
If we assume both parents are carriers, which is the minimum requirement for offspring to show the disease
PUNNET SQUARE
Monohybrid cross for PKU with heterozygote parents.
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Female parents gametes
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Male parents gametes
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P
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little p
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P
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PP ('normal')
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Pp (carrier)
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little p
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Pp (carrier)
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pp (affected)
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PP = 1 Genotypically homozygous, phenotypically normal
Pp=2 Genotypically heterozygous, phenotypically normal
pp=1 Genotypically homozygous, phenotypically affected
Determination of risk
Most commonly both parents would be heterozygotes (carriers rather than suffers)
1 in 4 of the offspring will be homozygous for the allele
2 in 4 will be carriers i.e heterozygotes
1 in 4 will be clear, i.e. will not have the allele at all
Update:
In the 1980's further evidence has been presented which suggests that this disease is not a strict case of the P allele being completely dominant.
It seems that even the carriers, i.e. Pp seem to have lower than normal IQ, suggesting the disease may have some incomplete dominance effects.
Overall, for AUTOSOMAL DOMINANT traits,
the possibility of any offspring expressing the trait is
- if 1 or more parents are homozygous Dominant 100%
- If 1 parent is homozygous dominant and 1 heterozygous 100%
- If Both are heterozygous 75%
- If 1 is homozygous recessive and 1 heterozygous 50%
- If both are homozygous recessive 0%
For AUTOSOMAL RECESSIVE traits
the possibility of any offspring expressing the trait is
- if 1 or more parents are homozygous Dominant 0%
- If 1 parent is homozygous dominant and 1 heterozygous 0%
- If Both are heterozygous 25%
- If 1 is homozygous recessive and 1 heterozygous 50%
- If both are homozygous recessive 100%
Most of us will be carriers of one or more deleterious recessive genes.
Matings between close relatives ('inbreeding') are much more likely to 'expose' deleterious recessives in offspring than are matings between unrelated individuals.