11.4 - Inheritance in Humans

Human Chromosomes and Karyotype

• Human somatic cells contain 44 autosomes and 2 sex chromosomes.
• Karyotype: The number and structure of chromosomes in a cell nucleus.
• Chromosomes in a karyotype are paired as homologous chromosomes according to size, centromere position and banding pattern.
• A complete karyotype is arranged from the largest and longest homologous pair to the smallest and shortest pair; the sex chromosomes are placed last.

Autosomes and Sex Chromosomes

• Autosomes:
  • Chromosome pairs 1 to 22.
  • Control all characteristics of somatic cells.
  • Examples: blood group, height and skin colour.
• Sex chromosomes:
  • Chromosome pair 23.
  • Carry genes that determine sex.
  • Male: $XY$; female: $XX$.
  • The $X$ chromosome is longer than the $Y$ chromosome; the $Y$ chromosome carries only genes involved in determining sex characteristics.

Nondisjunction and Abnormal Karyotypes

• Nondisjunction occurs when homologous chromosomes fail to separate during anaphase I or sister chromatids fail to separate during anaphase II.
• Nondisjunction can produce a gamete with 22 or 24 chromosomes; fertilisation with a normal gamete can produce a zygote with 45 or 47 chromosomes.
• Down syndrome:
  • 47 chromosomes; one extra chromosome at pair 21.
  • Also known as trisomy 21; occurs in males or females.
• Turner syndrome:
  • 45 chromosomes, $44+XO$.
  • One $X$ chromosome is missing; the individual is female.
• Klinefelter syndrome:
  • 47 chromosomes, $44+XXY$.
  • One extra $X$ chromosome; the individual is male.
  • Male secondary sex characteristics are not well developed.

Human Inheritance

ABO Blood Groups

• ABO blood groups are an example of multiple alleles.
• One gene has three alleles at one locus: $I^A$, $I^B$ and $I^O$; each individual carries only two alleles.
• These alleles determine the antigen on the surface membrane of red blood cells.
• $I^A$ and $I^B$ are dominant over the recessive $I^O$ and are codominant to each other.
• When $I^A$ and $I^B$ occur together, both effects are expressed as blood group AB.
• Blood group A: $I^A{I}^A$ or $I^A{I}^O$.
• Blood group B: $I^B{I}^B$ or $I^B{I}^O$.
• Blood group AB: $I^A{I}^B$.
• Blood group O: $I^O{I}^O$.
• Cross $I^A{I}^O\times I^B{I}^O$ produces $I^A{I}^B$, $I^A{I}^O$, $I^B{I}^O$ and $I^O{I}^O$ in a $1:1:1:1$ phenotypic ratio.

Rhesus Factor

• Antigen D on red blood cells is known as the Rhesus factor (Rh).
• Rhesus positive ($R{h}^{+}$): Rhesus factor is present; genotype $R{h}^{+}R{h}^{+}$ or $R{h}^{+}R{h}^{-}$.
• Rhesus negative ($R{h}^{-}$): Rhesus factor is absent; genotype $R{h}^{-}R{h}^{-}$.
• $R{h}^{+}$ is dominant and $R{h}^{-}$ is recessive.
• Cross $R{h}^{+}R{h}^{+}\times R{h}^{-}R{h}^{-}$ produces only Rhesus-positive offspring, $R{h}^{+}R{h}^{-}$.
• Cross $R{h}^{+}R{h}^{-}\times R{h}^{-}R{h}^{-}$ produces $\frac{1}{2}$ Rhesus-positive and $\frac{1}{2}$ Rhesus-negative offspring.

Thalassaemia

• Thalassaemia is an inherited disease caused by a gene mutation on an autosome, chromosome 11 or 16.
• Abnormal and reduced haemoglobin causes red blood cells to be smaller and paler.
• Thalassaemia minor: The carrier has one recessive thalassaemia allele but no symptoms; detection requires a blood test.
• Thalassaemia major: The patient has both recessive alleles.
• Symptoms include tiredness, paleness, breathing difficulty and changes in facial bone formation from 3 to 18 months of age.

Sex Determination

• Male genotype: $44+XY$; female genotype: $44+XX$.
• Sperms are haploid and carry either $22+X$ or $22+Y$.
• Secondary oocytes are haploid and carry $22+X$.
• Fertilisation:
  • $(22+X)+(22+X)\to 44+XX$ (female).
  • $(22+Y)+(22+X)\to 44+XY$ (male).
• Expected phenotypic ratio: $1$ female : $1$ male.

Sex-linked Inheritance

• Sex-linked genes are located on sex chromosomes, control specific characteristics and do not determine sex.
• Colour blindness and haemophilia are caused by recessive genes linked to the $X$ chromosome.
• The $Y$ chromosome is shorter and has fewer alleles than the $X$ chromosome; in males, a dominant or recessive allele on the single $X$ chromosome is expressed.

Colour Blindness

• Colour blindness is the inability to distinguish specific colours, usually red and green; most affected individuals are male.
• $X^B$: dominant allele for normal colour vision; $X^b$: recessive allele for colour blindness.
• Females: $X^B{X}^B$ normal; $X^B{X}^b$ normal carrier; $X^b{X}^b$ colour blind.
• Males: $X^{B}Y$ normal; $X^{b}Y$ colour blind.
• Cross $X^{B}Y\times X^B{X}^b$ produces $X^B{X}^B$, $X^B{X}^b$, $X^{B}Y$ and $X^{b}Y$ in a $1:1:1:1$ phenotypic ratio.

Haemophilia

• Haemophilia is the inability of blood to clot normally due to a lack of blood-clotting factor; excessive internal or external bleeding may be fatal.
• $X^H$: dominant allele; $X^h$: recessive allele.
• Females: $X^H{X}^H$ normal; $X^H{X}^h$ carrier; $X^h{X}^h$ haemophilic.
• Males: $X^{H}Y$ normal; $X^{h}Y$ haemophilic.
• Cross $X^{H}Y\times X^H{X}^h$ produces $X^H{X}^H$, $X^H{X}^h$, $X^{H}Y$ and $X^{h}Y$ in a $1:1:1:1$ phenotypic ratio.

Ability to Roll the Tongue and Types of Earlobe

• The ability to roll the tongue is a dominant trait.
• A free earlobe is dominant over an attached earlobe.
• Both characteristics are inherited according to Mendel’s Law.

Family Pedigree

• A family pedigree or lineage is a flowchart through several generations showing ancestral relationships and inheritance of a characteristic from common ancestors to the present generation.
• Pedigree analysis enables geneticists to predict inheritance and identify whether a gene is dominant or recessive.
• A dominant gene normally appears in every generation; a recessive gene may be hidden in certain generations.
• Standard symbols:
  • Square: male; circle: female.
  • Unshaded: normal; shaded: affected.
  • Half-shaded circle: female carrier.
  • Horizontal line: marriage; vertical line: offspring.
  • Roman numerals: generations.