Inheritance
Genetic Counselling and Mendelian Inheritance
Terms
Phenotype: observable characteristic or trait (appearance, behaviour) expressed by genotype
Genotype: makeup of alleles (AA or Aa or aa)
Dominant: allele always expressed (Aa)
Recessive: allele expressed if both copies are identical (aa)
Genes are expressed simultaneously by two alleles
o One allele from each homologous chromosome
o Homozygous: two identical alleles (AA or aa)
o Heterozygous: different alleles (Aa)
Monohybrid Inheritance
Inheritance of a single characteristic
o Controlled by different alleles of the same gene
Autosomal recessive
o Example: Cystic Fibrosis, Phenylketonuria
- Normal allele is dominant
- To develop the disease, two abnormal alleles are required (homozygous)
- Carriers carry an abnormal allele but are not affected (heterozygous)
o Both parents are heterozygous carriers (Aa + Aa)
- 25% unaffected (AA)
- 50% carrier (Aa)
- 25% affected (aa)
o Affected (aa) + unaffected (AA)
- All offspring will be carriers
o Affected (aa) + Carrier (Aa)
- 50% carriers and 50% affected
Autosomal dominant
o Examples: Huntington's
- Abnormal allele is dominant
- To develop the disease, only one abnormal allele is required
- No unaffected carriers possible
o Aa + aa → 50:50
o Aa + Aa → 3:1 (75% affected and 25% unaffected)
Codominance
Example: Sickle-cell anaemia
o Mutation in β-globin chain of haemoglobin
o This forms haemoglobin S (HbS)
o Red blood cells become sickle shaped in low oxygen levels
- Reduces their flexibility
- Cannot deform to pass through capillaries
- May get stuck in small blood vessels
- Causes organ damage and ischaemia
o Abnormal red cells are destroyed by the spleen → anaemia
Heterozygous allele is neither dominant nor recessive
o Both alleles are expressed to determine phenotype
o Normal allele still produces 50% of normal haemoglobin (no symptoms)
o People are carriers and have a sickle-cell trait
Malaria
o Sickle-cell anaemia is more common in Africa due to malaria
o Those with sickle-cell trait are more resistant to malaria
o Red cells start to sickle when infected by malaria and rupture
o Malaria plasmodium is unable to reproduce in red cells
Inheritance
o Sickle-cell anaemia (SS) + Sickle-cell trait (AS)
- 50% carriers (AS)
- 50% affected (SS)
o Both parents have sickle-cell trait (AS)
- 25% unaffected (AA)
- 50% carrier (AS)
- 25% affected (SS)
Multiple Alleles
ABO blood group is controlled by the immunoglobulin gene I
o There are 3 alleles IA, IB, and I0 for that gene
o These alleles code for antigens A, B and neither A/B, respectively
Only 2 alleles can be present in a diploid cell
o IAIB is co-dominant
o I0 is recessive
Rhesus Blood Groups
Rhesus (Rh) positive
o Presence of antigen D on red cells
o Allele is dominant
Rh negative mother AND Rh positive baby
o First pregnancy
- Red cells CANNOT cross the placenta
- But mixing of blood does occur when giving birth
- Mother develops antibodies to antigen D (sensitisation)
o Second pregnancy
- Antibodies CAN cross the placenta
- Attack baby's red blood cells
- Causes haemolytic disease of the newborn (anaemia + jaundice, stillbirth)
Prevention
o Rh negative + not sensitized → give anti-D injection
o Anti-D destroys Rh positive cells before antibodies develop
o Given during pregnancy and after birth
Chi-Squared Test (x2)
Observed Expected value
o IMG
o degree of freedom = n - 1
Shows if differences between sets of data are significant or not
Null hypothesis states that there are no significant differences between sets of data
Small value / probability higher than the level of significance 0.05/5%
o Little difference between observed and expected value
o Likely to be extremes of the same population
o Null hypothesis accepted
Large value / probability is less than the level of significance 0.05/5%
o Significant difference between observed and expected data
o Likely to be two distinct populations
o Null hypothesis rejected
Genetic Counselling
Genetic screening
o Detect whether person is a carrier for an inherited disease
o Done by searching extracted DNA for the base-sequence of the gene
Chorionic villus sampling (CVS)
o Small sample of the placenta
o Performed after 10wks of pregnancy
o Thin needle through wall of abdomen or through vagina and opening of womb
Amniocentesis
o Small sample of amniotic fluid (fluid that surrounds foetus in womb)
o Performed between 15-22wks
o Passing needle through abdomen and womb
o Amniotic fluid is drawn out through a syringe
o Cells in fluid are cultured and DNA is extracted
Karyotyping
o Arrangement of chromosomes into homologous pairs
o Detect abnormal chromosomes (not genes)
Embryo screening
o Only allowed for severe genetic diseases
o Embryos are cultured using IVF
o Single cell is taken with a pipette and its DNA extracted
o (-) Produces many embryos which are not used
o (-) Long-term side effects for the embryo used are not known
Sex-linked Inheritance
Inheritance of sex in humans
o Females are homogametic sex (X: or XX)
o Males are heterogametic sex (XY) / Y chromosome is shorter
o Involves whole chromosomes instead of individual genes
Phenotypic characteristic is inherited on X, not on Y chromosome
o Characteristic is more common in males → females can be heterozygous (XAXB)
o Sex linked characteristic is never passed from father to son
Example: Duchenne muscular dystrophy (DMD)
o Faulty gene prevents production of dystrophin
o The protein is normally found in muscles and holds cells together
o Lack of dystrophin causes progressive muscle weakness
o Muscle is eventually replaced by fat and connective tissue
X-linked recessive
o Normal allele is dominant (X)
o Female carrier (Xx) + Unaffected male (YX)
- Offspring phenotype and genotype
- 25% affected son (Yx)
- 25% unaffected son (YX)
- 25% female carrier (Xx)
- 25% unaffected daughter (XX)
Therefore
- 50% affected male
- 50% female carrier
Only males can be affected
All daughters of affected male will be carrier
All sons of affected male are unaffected
o Female carrier (Xx) + Affected male (Yx)
- 25% healthy son, female carrier, affected son and affected daughter
o Female unaffected (XX) + Affected male (Yx)
- 50% healthy (YX) and 50% carrier (Xx)
- No male to male transmission
- Females are always carriers
Inheritance
Gene Interactions - Co-dominance, Multiple Alleles, Epistasis, etc
The Biology Project - Information on Monohybrid/Dihybrid Crosses
Drag and Drop Genetics- Interactive Exercises on Crosses