GENETICS

LEARNING OBJECTIVES
Classify genetic disorders
Describe mutations

TERMINOLOGY
hereditary :
Inherited from parents
familial :
Transmitted in the gametes through generations
congenital :
present at birth (not always genetically determined - e.g.
congenital syphilis, toxoplasmosis)
! not all genetic diseases are congenital - e.g. Huntington
disease - 3rd to 4th decade of life

INTRODUCTION
Normal human cells contain 23 pairs of
chromosomes
This includes one pair of sex chromosome XX or XY
During cell division we can identify chromosomes

WHAT ARE
MUTATIONS?
The term mutation refers
to permanent
transmissable changes in
the DNA.
May occur in somatic cells
(arent passed to
offspring)
May occur in gametes
(eggs & sperm) and be
passed to offspring

TYPES OF GENE
MUTATIONS
Include:
Point Mutations (Substitutions)
Missense (another amino acid substituted)
Nonsense (Causes stop codon)

Frameshift mutations
Insertions
Deletions

GENE MUTATIONS
Point Mutations changes in one
or a few nucleotides
Substitution
THE FAT CAT ATE THE RAT
THE FAT HAT ATE THE RAT
Insertion
THE FAT CAT ATE THE RAT
THE FAT CAT XLW ATE THE RAT
Deletion
THE FAT CAT ATE THE RAT
THE FAT ATE THE RAT

GENE MUTATIONS
Frameshift Mutations
shifts the reading frame
of the genetic message so
that the protein may not
be able to perform its
function.
Insertion

THE FAT CAT ATE THE RAT

H
THE FAT HCA TAT
ETH ERA T

Deletion
THE FAT CAT ATE THE RAT
TEF ATC
H ATA TET GER AT

GENE MUTATION
ANIMATION

CLASSIFICATION
3 groups of genetic diseases
1. Monogenic/ Single gene (Mendelian) disorders
2. Chromosomal aberrations (Cytogenetic disorders)
3. Disorders with multifactorial inheritance (polygenic)

GENETIC DISORDERS
Single gene
- Dominant/recessive pedigree patterns (Mendelian inheritance).
- Can affect structural proteins, enzymes, receptors, transcription factors.

Chromosomal
- Thousands of genes may be involved.
- Multiple organ systems affected at multiple stages in gestation.
- Usually de novo (trisomies, deletions, duplications) but can be inherited
(translocations).

Multifactorial
- Environmental influences act on a genetic predisposition to
produce a liability to a disease.
- One organ system affected.
- Person affected if liability above a threshold.

Chromosomal disorders

NORMAL FEMALE KARYOTYPE (46,

XX)
(G BANDING)

DEFINING CHROMOSOMAL
LOCATION
Arm

Region Band Subband

2
1

2
1
1

1
2

1
2

q
3
2
Chromosome 17

3
2
1
2
1
5
4
3
2
1

3
1
2
3
1
2, 3
4
1
2
3

17q11.2

CONTINUE
Haploid: set of 23 chromosomes
Diploid: normal number of 46 chromosomes
Aneuploidy: less than an even multiple of 23 usually is
45 or 47 and rarely 48,49
Triploidy: 69 chromosomes
Mosaicism:

Mosaicism is a term used to describe the presence of

two or more populations of cells with different complements of
chromosomes
in the same individual.

CAUSE:
NONDISJUNCTION
Failure of
chromosomes to
separate during
meiosis
Causes gamete to
have too many or
too few
chromosomes

NUMERIC ABNORMALITIES
Autosomal:
Downs syndrome, Edward, Patau
Cri Du Chat

Sex chromosome related

Turners
Klinefelters

1. CHROMOSOME NUMBER
ABNORMALITY
TRISOMY 21 (47, XX, +21)

2. CHROMOSOME STRUCTURE
ABNORMALITIES

Translocation

Deletion

Derivative
chromosome

Inversion

Insertion

Isochromosome

Ring
chromosome

Translocations: When a portion of one chromosome is

transferred to another chromosome.

CHROMOSOME
MUTATIONS

Deletion
Inversion
Translocation
Duplication

DELETION
Due to breakage
A piece of a
chromosome is lost

INVERSION
Chromosome segment
breaks off
Segment flips around
backwards
Segment reattaches

TRANSLOCATION
Involves two
chromosomes that
arent homologous
Part of one
chromosome is
transferred to
another
chromosomes