Wk 12 – “The Wine Dark Sea”: Learning Objectives:
Genetic Disease:
1. Describe the range of patterns of heredity and distribution that may occur with genetic
disease and provide examples.
Modes of inheritance
 Autosomal dominant
 Autosomal recessive
 X-linked
 Multifactorial
 Chromosomal disorders
Autosomal dominant inheritance
Where the impact of having a faulty gene copy on one chromosome and a working gene copy
on the partner chromosome is such that the cell cannot work properly, the mutation making
the gene faulty is described as dominant
• Expressed in the heterozygote. ie.
 With respect to a particular trait or condition, an individual who has inherited two
different alleles, usually one normal and the other abnormal, at a particular locus.
 Heterozygous refers to having inherited different forms of a particular gene from each
parent
• Females, males equally affected (unless sex limited). Females and males transmit equally.
• Risk to offspring of an affected person is 1 in 2
• Vertical pattern of inheritance
• Variability in expression (expressivity = variability of phenotype within same mutation
“family”)
• Incomplete penetrance (penetrance = proportion of mutation carriers who show the
phenotype).
• New mutations common. Homozygosity rare - may be a different disorder.
Examples: Huntington disease, familial hypercholesterolaemia and inherited predisposition to
bowel, breast and ovarian cancers
Autosomal recessive inheritance
An autosomal recessive disorder means two copies of an abnormal gene must be present in
order for the disease or trait to develop. People with only one defective gene in the pair are
considered carriers. However, they can pass the abnormal gene to their children.
• Manifest in the homozygote ie:
 With respect to a particular trait or condition, an individual who has inherited
identical alleles at a particular locus
 An organism that has two identical alleles of a gene.
• Males and females equally likely to be affected.
• Birth of an affected establishes both parents as carriers
• Commonly severe disorders
• May recur in sibship – “horizontal” pattern
• Risk to siblings of affected is 1:4 (25%)
• Increased in consanguineous (relating to or involving persons (as first cousins) that are
relatively closely related) unions.
Examples:
Cystic fibrosis, Thalassaemia (alpha/beta), Phenylketonuria (PKU),
Oculocutaneous albinism, Congenital deafness (many).
X-linked Inheritance
X-linked inheritance - the pattern of inheritance of a condition caused by a faulty gene on the
X chromosome. The faulty gene may be recessive or dominant. There are very few genes
located on the Y chromosome. Women XX, Men XY.
• Male to male transmission never occurs
• All daughters of an affected male will receive the gene
• Unaffected males never transmit the disease to descendants of either sex
• Risk to sons of women who are definite carriers is 50%
• Risk of carrier status for daughters of carriers is 50%
• Affected homozygous females are exceptional in X-linked recessive disorders - possible if
an affected male marries a carrier female
• X-linked recessive/ X-linked dominant – terms with limited usefulness
Examples:
Duchenne Muscular Dystrophy, Haemophilia A (and B), Fragile X syndrome,
X-SCID
Multifactorial inheritance
Where "many factors" (multifactorial) are involved in causing a birth defect. The factors are
usually both genetic and environmental, where a variable combination of genes from both
parents, in addition to unknown environmental factors, produce the trait or condition.
 Generally multiple genes (oligo, polygenic).
 Variable combination of genes and environment
 Accounts for most disease (infectious disease influenced by host genetic factors,
trauma by male sex, character traits with genetic contribution)
 Complex, empiric data needed for genetic counselling
Examples:
Cleft lip/palate, Pyloric stenosis, Congenital heart disease, Neural tube defects
Ischaemic heart disease
Chromosomal Disorders
Various mechanisms. Consequences of genomic imbalance.
Numerical Anomalies:
 Extra chromosomes Trisomy 21 (Down syndrome) Trisomy 18 (Edward syndrome)
Trisomy 13 (Patau syndrome) XXY (Klinefelter syndrome
 Missing chromosomes 45,X (Turner syndrome) (monosomy - usually lethal)
Structural Anomalies
 Translocations (reciprocal, Robertsonian)


Deletions (visible and submicroscopic)
Inversions
2. Distinguish between congenital and genetic disease
Congenital diseases may be related to genomic mutations but are not passed on via germ cells
(gametes / sex cells). Rather these mutations (permanent changes in DNA) occur in somatic
cells and may cause cancers or other malformations. Congenital diseases develop during
prenatal life and are evident at birth or in early infancy. They may not become apparent til
later life. May or may not be hereditary.
Genetic diseases are caused by abnormalities of the genetic material within the germ cells.
Not always hereditary. New mutations can occur. Genetic disorders involve a permanent
change (or mutation) in the genome. A genetic disorder can involve a single-gene trait,
multifactorial inheritance, or a chromosome disorder.
3. Outline the concepts of gene/carrier frequencies, selection pressures for heterozygous
carriers for recessive diseases.
Gene or allele frequency measures the frequency in the population of a particular gene
relative to other genes at its locus. Expressed as a proportion (between 0 and 1) or percentage
(between 0 and 100%). In the simplest case, gene frequency is measured by counting the
frequencies of each gene in the population. If a genotype contains two genes, then there are a
total of 16 genes per locus in a population of eight individuals:
Aa AA aa aa AA Aa AA Aa. In this population, then:
Frequency of A = 9/16 = 0.5625
Frequency of a = 7/16 = 0.4375.
Carrier frequency = The proportion of individuals in a population who have inherited a single
copy of a specific recessive gene mutation
Selection Pressures: environmental factors which may reduce reproductive success in a
population and thus contribute to evolutionary change or extinction through the process of
natural selection.