Transcript Introduction to Medical Genetics

Introduction to Medical
Genetics
Fadel A. Sharif
Contact details
 Medical
Technology Department
 Genetics
lab
 [email protected]

Textbook:


Genetics in Medicine, 7th edition. Nussbaum, McInnes
& Willard. W.B. Saunders Co. (2007).
Reference

Emery’s Elements of Medical Genetics, 13th edition,
Turnpenny & Ellard. Churchill Livingstone. (2007).
Grades

Midterm exam
30%
 Assignments, participation & quizzes 10%

Final exam
60%
Topics

1: Introduction
 2: Patterns of Single-Gene Inheritance
 3: Genetic Variation in Individuals
 4: Genetic Variation in Populations
 5: Gene Mapping
 6: Principles of Clinical Cytogenetics
 7: Clinical Cytogenetics: Disorders of the Autosomes and
the Sex Chromosomes
 8: Treatment of Genetic Diseases
 9: Genetics and Cancer
 10: Prenatal Diagnosis
Glossary & Definitions
 Genetics
is concerned with variation and
heredity in all living organisms
 Human genetics is the science of
variation and heredity in humans
 Medical genetics deals with human
genetic variation of significance in
medical practice and research
 Cytogenetics: the study of chromosomes
Glossary & Definitions

Genomics: the study of genome, its
organization and functions
 Population genetics: genetic variation in
human populations and factors that affect
allele frequencies
 Clinical genetics: application of genetics to
diagnosis and patient care
 Genetic counseling: risk information,
psychological and educational support to
patients and/or their families
Glossary & Definitions
 Genotype
- the genetic constitution of
the organism
 Phenotype
- the observable expression
of genotype
Glossary & Definitions

Locus - a chromosomal location

Alleles - alternative forms of the same locus

Mutation - a change in the genetic material,
usually rare and pathological

Polymorphism - a change in the genetic
material, usually common and not necessarily
pathological
Glossary and Definitions
 Homozygote - an organism with two identical
alleles
 Heterozygote - an organism with two different
alleles
 Hemizygote - having only one copy of a gene

Males are hemizygous for most genes on the sex
chromosomes
Glossary and Definitions
 Dominant
trait - a trait that shows in a
heterozygote
 Recessive
heterozygote
trait - a trait that is hidden in a
Family history is important
It can be critical in diagnosis
 Can provide info about natural history of
the disease & variation in its expression
 Can clarify pattern of inheritance


Note:
Diagnosis of a hereditary condition allows risk
estimation in other family members so that
proper management, prevention, & counseling
can be offered to patient & family
Role of Genes in Human Disease

Most diseases / phenotypes result from the interaction
between genes and the environment

Some phenotypes are primarily genetically determined
 Achondroplasia

Other phenotypes require genetic and environmental
factors
 Mental retardation in persons with PKU

Some phenotypes result primarily from the environment
or chance
 Lead poisoning
Major types of genetic
disease
 Chromosomal
 Single
disorders
gene disorders
 Polygenic
diseases
Chromosomal disorders
 Addition
or deletion of entire
chromosomes or parts of chromosomes.
Rearrangement of chromosomal segments
 Typically
 Classic
more than 1 gene involved
example is trisomy 21 - Down
syndrome
Down Syndrome
Single gene disorders
 Single
mutant gene has a large effect on
the patient
 Transmitted in a Mendelian fashion
 Autosomal dominant, autosomal
recessive, X-linked, Y-linked
 Osteogenesis imperfecta - autosomal dominant
 Sickle cell anemia - autosomal recessive
 Haemophilia - X-linked
Autosomal dominant pedigree
Polygenic diseases

The most common yet still the least understood
of human genetic diseases

Result from an interaction of multiple genes,
each with a minor effect

The susceptibility alleles are common

Type I and type II diabetes, autism, multiple
sclerosis
Polygenic disease pedigree
Identifying disease genes has
been revolutionized by the
sequencing of the
Human Genome
The sequence
 3.3
billion base pairs
 Gene
 This
prediction ~ 25,000
is likely to be an underestimation due
to the occurrence of regulatory RNAs
Accessing the sequence
 Public
databases
 Freely
available
 Continuously
modified and updated
www.ensembl.org
Searching for FRZB
FRZB is located on chromosome 2
FRZB transcript sequence
Two common amino acid substitutions
in FRZB