Medical genetics

Chapter1
Introduction to Genetics
Lecturer: Ahmed Elmi PhD Candidate
Bs: Medical Lab
Msc: molecular medicine
Candidate PhD molecular medicine
 Genetics
• Genetics in medical science had its start at the beginning of the 20th century,
with the recognition by Garrod and others that Mendel’s laws of inheritance
could explain the recurrence of certain disorders in families.

• During the ensuing 100 years, medical genetics grew from a small subspecialty
concerned with a few rare hereditary disorders to a recognized medical
specialty whose concepts and approaches are important components of the
diagnosis and management of many disorders, both common and rare.
• This is even more the case now at the beginning of the 21st
century, with the completion of the Human Genome Project,
an international effort to determine the complete content of
the human genome, defined as the sum total of the genetic
information of our species (the suffi x -ome is from the Greek
for “all” or “complete”). We can now study the human
genome as an entity, rather than one gene at a time.
• Medical genetics has become part of the broader field of
genomic medicine, which seeks to apply a large-scale
analysis of the human genome, including the control of gene
expression, human gene variation, and interactions between
genes and the environment, to improve medical care.
• Medical genetics focuses not only on the patient but also on the entire
family. A comprehensive family history is an important first step in the
analysis of any disorder, whether or not the disorder is known to be genetic.

• As pointed out by Childs, “to fail to take a good family history is bad
medicine.”

• A family history is important because it can be critical in diagnosis, may

show that a disorder is hereditary, can provide information about the
natural history of a disease and variation in its expression, and can clarify
the pattern of inheritance
• Genetics is rapidly becoming a central organizing principle in medical practice.

• Here are just a few examples of the vast array of applications of genetics and
genomics to medicine today:

• A child who has multiple congenital malformations and a normal routine

chromosome analysis undergoes a high-resolution genomic test for
submicroscopic chromosomal deletions or duplications.
• A young woman with a family history of breast cancer receives education, test
interpretation, and support from a counselor specializing in hereditary breast
cancer.

• A hematologist combines family and medical history with gene testing of a

young adult with deep venous thrombosis to assess the benefits and risks of
initiating and maintaining anticoagulant therapy.
 What is Genetics?
• Genetics - The study of heredity

• Genes - set of characteristics inherited from your

parents
• Found on chromosomes and contain DNA

• Recent discoveries on how characteristics are passed

from generation to generation
 What is meant by Medical Genetics?

• Medical genetics is the specialty of medicine that involves the

diagnosis and management of hereditary disorders, i.e. it refers to the
application of genetics to medical care. So, diagnosis, management,
and counseling of individuals with genetic disorders as well as
research on the causes and inheritance of genetic disorders would be
considered part of medical genetics.
• Genetic medicine is a newer term for medical genetics and incorporates
areas such as gene therapy, personalized medicine, and the rapidly
emerging new medical specialty, predictive medicine and laboratory
 Various specialties within medical genetics are interrelated:

1. Clinical Genetics.

2. Cytogenetics.

3. Molecular Cytogenetics.

4. Molecular Genetics

5. Human genetics, molecular biology, genetic engineering, or biotechnology.

• Human diseases in general, whether medical or surgical, can roughly
be classified into three categories:

1. Those that are genetically determined.

2. Those that are almost entirely environmentally determined.

3. And those to which both nature and nurture contribute.

• However, progress in understanding the molecular basis of many so-
called environmental disorders had tended to blur these distinctions.
At one time, microbial infections were cited as examples of disorders
arising wholly from environmental influences, but it is now clear that
to a considerable extent, an individual's genetic makeup influences his
or her immune response and susceptibility to microbiologic infections.
Classification of Genetic disorders (important):

1. Classical Genetic Diseases:

a. Chromosomal (Cytogenetic) disorders.

b. Single gene (or unifactorial) disorders (Mendelian Disorders).

c. Multifactorial disorders.
2. Non-Classical Diseases "or the single gene disorders with atypical pattern of
inheritance":

a. Diseases caused by mutations in mitochondrial genes.

b. Triplet repeat mutations.

c. Uniparental disomy.

d. Genomic imprinting.

e. Gonadal mosaism.

Added to that, is a large group of disorders "malformations" that manifest at birth, called
congenital malformations, that many of them are caused by genetic disorders.
 Types of Genetic Disease

• Chromosomal

• Single gene---Mendelian

• Multifactorial---common complex diseases

• Somatic cell ---cancers

What Do Medical Geneticists Do?

Diagnosis and treatment of genetic disease

Presymptomatic testing for genetic disease

Carrier testing, especially for high risk people

Genetic counseling during pregnancy

 Genetic Evaluation: Data gathering

History, especially family history

Physical examination - major and subtle findings

Pattern recognition

Laboratory testing – EMG,(electromyography) DNA

 Genetic Evaluation/Counseling Issues
Patient education and treatment
Natural history

Risk of occurrence/re-occurrence

Possibilities for diagnosis and treatment of symptoms

Impact on the individual and family

 Ethical Issues
Protection of the individual’s right to privacy and fair treatment (Autonomy
and privacy)

Competing demands of family members or mothers and fetuses (Privacy,

equity and justice)

Justification of exposure to increased risks (Beneficence)

 Terminology
hereditary = derived from parents

familial = transmitted in the gametes through generations

congenital = present at birth (not always genetically determined - e.g.

congenital syphilis, toxoplasmosis)

! not all genetical diseases are congenital - e.g. Huntington disease - 3rd
to 4th decade of life
 Classification
3 groups of genetic diseases

1. Disorders with multifactorial inheritance (polygenic)

2. Monogenic (mendelian) disorders

3. Chromosomal aberrations
 Mendelian Genetics

• A number of hypotheses were suggested to explain heredity, but Gregor

Mendel, was the only one who got it more or less right.

• His early adult life was spent in relative obscurity doing basic genetics
research and teaching high school mathematics, physics, and Greek in
Brno (now in the Czech Republic).
 Genes and Dominance
Mendel studied 7 different pea plant traits.

Trait: specific characteristic (ex: color)

Mendel’s traits were contrasting

Original pair of plants is called “parent”, or simply P

Offspring are called F1 for “first filial”

The offspring of crosses between parents with different traits are called
hybrids.
 What were F1 hybrid plants like?
• All of the offspring had the trait of only one of the parents.
 Mendel’s Conclusions
• 1. Inheritance is determined by chemical factors that determine traits and are
passed from one generation to the next. These chemical factors are called genes.
• Each of the traits was controlled by one gene that occurred in contrasting forms.

• These different forms are called alleles.

• 2. Principle of Dominance: Some alleles are dominant while others are recessive
• Dominant allele always expressed unless there are two recessive alleles

• Example: In peas, tall is dominant while short is recessive; yellow dominant, green
recessive
 Definitions
• Allele- discrete version of the same gene

• Genotype- the genes of an organism for one specific trait

• Phenotype- the physical appearance of a trait in an organism

 Definitions
• Dominant trait refers to a genetic feature that “hides” the recessive trait in the
phenotype of an individual.
• The term "recessive” describes a trait that is covered over (or dominated) by
another form of that trait and seems to disappear.
• Homozygous= two alleles that are the same for a trait (Pure)

• Heterozygous= two different alleles for a trait (Hybrid)

 •End
•Any question