Introduction to Medical Introduction to Medical GeneticsGenetics

Fadel A. SharifFadel A. Sharif

Contact detailsContact details

Medical Technology DepartmentMedical Technology Department

Genetics labGenetics lab

fsharif@iugaza.edufsharif@iugaza.edu

Textbook:Textbook: Genetics in Medicine, 7Genetics in Medicine, 7thth edition. Nussbaum, McInnes edition. Nussbaum, McInnes

& Willard. W.B. Saunders Co. (2007).& Willard. W.B. Saunders Co. (2007).

ReferenceReference Emery’s Elements of Medical Genetics, 13Emery’s Elements of Medical Genetics, 13thth edition, edition,

Turnpenny & Ellard. Churchill Livingstone. (2007). Turnpenny & Ellard. Churchill Livingstone. (2007).

GradesGrades

Midterm examMidterm exam 30%30% Assignments, participation & quizzesAssignments, participation & quizzes 10%10% Final examFinal exam 60%60%

TopicsTopics

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 & DefinitionsGlossary & 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 & DefinitionsGlossary & Definitions

Genotype - the genetic constitution of Genotype - the genetic constitution of the organismthe organism

Phenotype - the observable expression Phenotype - the observable expression of genotypeof genotype

Glossary & DefinitionsGlossary & Definitions

LocusLocus - a chromosomal location - a chromosomal location

AllelesAlleles - alternative forms of the same locus - alternative forms of the same locus

MutationMutation - a change in the genetic material, - a change in the genetic material, usually rare and pathologicalusually rare and pathological

PolymorphismPolymorphism - a change in the genetic - a change in the genetic material, usually common and not necessarily material, usually common and not necessarily pathologicalpathological

Glossary and DefinitionsGlossary and Definitions

HomozygoteHomozygote - - an organism with two identical an organism with two identical allelesalleles

HeterozygoteHeterozygote - an organism with two different - an organism with two different allelesalleles

HemizygoteHemizygote -- having only one copy of a genehaving only one copy of a gene Males are hemizygous for most genes on the sex Males are hemizygous for most genes on the sex

chromosomeschromosomes

Dominant traitDominant trait -- a trait that shows in a a trait that shows in a heterozygoteheterozygote

Recessive traitRecessive trait - a trait that is hidden in a - a trait that is hidden in a heterozygoteheterozygote

Glossary and DefinitionsGlossary and Definitions

Family history is importantFamily history is important

It can be critical in diagnosisIt can be critical in diagnosis Can provide info about natural history of Can provide info about natural history of

the disease & variation in its expressionthe disease & variation in its expression Can clarify pattern of inheritanceCan clarify pattern of inheritance

Note:Note:

Diagnosis of a hereditary condition allows risk Diagnosis of a hereditary condition allows risk estimation in other family members so that estimation in other family members so that proper management, prevention, & counseling proper management, prevention, & counseling can be offered to patient & familycan be offered to patient & family

Role of Genes in Human DiseaseRole 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 Major types of genetic diseasedisease

Chromosomal disordersChromosomal disorders

Single gene disordersSingle gene disorders

Polygenic diseasesPolygenic diseases

Chromosomal disordersChromosomal disorders

Addition or deletion of entire chromosomes Addition or deletion of entire chromosomes or parts of chromosomes. Rearrangement or parts of chromosomes. Rearrangement of chromosomal segments of chromosomal segments

Typically more than 1 gene involvedTypically more than 1 gene involved

Classic example is trisomy 21 - Down Classic example is trisomy 21 - Down syndromesyndrome

Down SyndromeDown Syndrome

Single gene disorders Single gene disorders

Single mutant gene has a large effect on Single mutant gene has a large effect on the patientthe patient

Transmitted in a Mendelian fashionTransmitted in a Mendelian fashion Autosomal dominant, autosomal Autosomal dominant, autosomal

recessive, X-linked, Y-linkedrecessive, X-linked, Y-linked Osteogenesis imperfecta - Osteogenesis imperfecta - autosomal dominantautosomal dominant

Sickle cell anemia - Sickle cell anemia - autosomal recessiveautosomal recessive

Haemophilia - Haemophilia - X-linkedX-linked

Autosomal dominant pedigreeAutosomal dominant pedigree

Polygenic diseasesPolygenic diseases

The most common yet still the least understood The most common yet still the least understood of human genetic diseasesof human genetic diseases

Result from an interaction of multiple genes, Result from an interaction of multiple genes, each with a minor effecteach with a minor effect

The susceptibility alleles are commonThe susceptibility alleles are common

Type I and type II diabetes, autism, multiple Type I and type II diabetes, autism, multiple sclerosissclerosis

Polygenic disease pedigreePolygenic disease pedigree

Identifying disease genes has Identifying disease genes has been revolutionized by the been revolutionized by the

sequencing of the sequencing of the Human Genome Human Genome

The sequenceThe sequence

3.3 billion base pairs3.3 billion base pairs

Gene prediction ~ 25,000Gene prediction ~ 25,000

This is likely to be an underestimation due This is likely to be an underestimation due to the occurrence of regulatory RNAsto the occurrence of regulatory RNAs

Accessing the sequenceAccessing the sequence

Public databasesPublic databases

Freely availableFreely available

Continuously modified and updatedContinuously modified and updated

www.ensembl.orgwww.ensembl.org

Searching for FRZBSearching for FRZB

FRZB is located on chromosome 2FRZB is located on chromosome 2

FRZB transcript sequenceFRZB transcript sequence

Two common amino acid substitutions Two common amino acid substitutions in FRZBin FRZB