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 (aren’t 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 mutationsInsertionsDeletions

GENE MUTATIONS

Point Mutations – changes in one or a few nucleotidesSubstitutionTHE FAT CAT ATE THE RATTHE FAT HAT ATE THE RAT

InsertionTHE FAT CAT ATE THE RATTHE FAT CAT XLW ATE THE RAT

DeletionTHE FAT CAT ATE THE RATTHE 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 THE FAT HCA TAT ETH ERA T

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

H

H

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)

p

q

Arm Region Band Subband

2

1

1

2

21

1

12

3

4

3212154321

12

312312, 34123

17q11.2

Chromosome 17

DEFINING CHROMOSOMAL LOCATION

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, PatauCri Du Chat

Sex chromosome relatedTurners Klinefelters

1. CHROMOSOME NUMBER ABNORMALITY

TRISOMY 21 (47, XX, +21)

Translocation Deletion

Insertion

Inversion Isochromosome

Ringchromosome

Derivativechromosome

2. CHROMOSOME STRUCTURE ABNORMALITIES

Translocations: When a portion of one chromosome is transferred to another chromosome.

CHROMOSOME MUTATIONS

DeletionInversionTranslocationDuplication

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 aren’t homologous Part of one chromosome is transferred to another chromosomes