Transcript Pedigree Drawing

Medical Genetics
Textbooks:
“Emery’s Elements of Medical genetics”
Strachan & Read “Human Molecular
Genetics” (for the genome project material)
Medical Genetics 1
• Causes of human disease: age,
environment, genetic factors and
combinations of these
• Using a combination of approaches, rapid
progress is now being made in our
understanding of the cause of many
genetic diseases
Classification of Genetic Disease
• I - Single gene disorders: Currently over
6,000 different disorders or traits
described, including:
– Cystic fibrosis
– Fragile X mental retardation
– Predisposition to colorectal cancer
• 30,000 different structural genes coded for
in the human genome.
Classification of Genetic Disease
• II - Chromosomal abnormalities
– 1959 - trisomy 21 found to be associated with
Down syndrome
• III - Multifactorial disease:
– Cleft lip and palate
– Insulin dependent diabetes mellitus
– Ischaemic Heart disease
– Cancer
Pedigrees and Inheritance
• To begin investigating the genetics of a
particular disorder:
– Observe the way condition is transmitted from
one generation to the next
– Study its frequency among relatives
Pedigree Drawing
Normal male
Affected male
Normal female
Affected female
Index case
Mating
Consanguineous mating (usually between cousins)
Parents with son and daughter (in order of birth)
Dizygotic twins
Monozygotic twins
Sex unspecified
Heterozygotes for autosomal genes
Carrier of X-linked genes
Dead
Miscarriage
Woman with children by different partners
Numbering of pedigree: generations I, II,
III….
Individuals in each generation 1, 2, 3,….
Mendelian Inheritance
• Autosomal Inheritance: due to a mutation
in a gene from chromosome 1 to 22
• Sex-linked Inheritance: gene on the X (or
Y) chromosome
• Either type may be dominant or recessive
Autosomal
Recessive
inheritance
Autosomal dominant inheritance
• an affected
person usually
has one affected
parent
• transmitted by
either sex
• child of an
affected parent is
at 50% risk of also
being affected
X-linked dominant inheritance
• affects either sex but more females than males
• females often more mildly affected than males
• child of an affected female at 50% chance of
being affected
• for an affected male, all his daughters but none
of his sons affected
• Quite rare, examples include an inherited form
of rickets (mutation in an endopeptidase gene)
X-linked dominant inheritance
Y-linked inheritance
•
•
•
•
affects only males
always have an affected father
all sons of affected man will be affected
no such diseases known, only
characteristics such as subfertility and
hairy ears
Mitochondrial inheritance
• mutations in mitochondrial genome
• maternal inheritance as fathers do not
pass mitochondria to their children
• wide clinical variation due to heteroplasmy
(mixture of normal and mutant
mitochondria)