Genetic Basis for Rare

Diseases

Dr Yassin Khaled
Learning Outcomes
• To Identify the general classes of genetic diseases
• Chromosomal abnormalities
• Monogenic (single gene) diseases
• Polygenic (multiple gene) diseases
• Multifactorial (complex) diseases

• To identify selected examples for each class of genetic diseases

Genomic Basis of Genetic Diseases
• Chromosomal abnormalities
• Monogenic (single gene) diseases
• Polygenic (multiple gene) diseases
• Multifactorial (complex) diseases
Chromosomal Abnormalities (Cytogenetic
Disorders)
• Due to defect in chromosome or
part of a chromosome
• Karyotype
• It is an individual’s complete set of
chromosomes
• Also refers to a laboratory produced
image of a person’s chromosomes
isolated from an individual cell and
arranged in numerical order
• A karyotype may be used to look for
abnormalities in chromosome
number or structure
Chromosomal Abnormalities (Cytogenetic
Disorders)
• To do karyotype
• Genetic material is extracted from the nucleus when the cell at
prometaphase (during sell division)
• At this stage, the genetic material is condensed and appear as road
shape structure called chromosomes
• Thus each chromosome can be easily identified
Major Types of Chromosomes based on the
location of centromere
How to distinguish between chromosomes??
• Banding Technique
• Chromosomes can be stained using different techniques
• For example
• Gimsa stain, where each chromosome shows distinct alternate
light and dark bans
• These bands can be used to localize different regions along
chromosomes
• Each arm is divided into numbered regions (e.g. 1. 2, 3. …) from
centromere outward
• In each region the bands are numerically ordered
• For example, 2q34 refers to:
• Chromosome 2, long arm, region3 and band 4
Banding Technique …
Chromosomal Abnormalities (Cytogenetic
Disorders) …
• A. Numerical: change in the number of chromosomes
• B. Structural: change in chromosome structure due to breakage
followed by loss or rearrangement of material
A. Numerical: change in the number of
chromosomes
A. Numerical: change in the number of
chromosomes …
A. Numerical: change in the number of
chromosomes …
A. Numerical: change in the number of
chromosomes …
B. Structural Abnormalities
B. Structural Abnormalities …
B. Structural Abnormalities …
Cytogenic Disorders Examples
2. Monogenic (Single-Gene) Diseases
Monogenic (Single-Gene) Diseases
• Disease caused by variants in one gene
• Often classified by
• Type (autosome or sex chromosome)
• Disease phenotype (dominant or recessive)
• Often studied via family studies (i.e. pedigrees or family trees)
Mode of Inheritance of Single gene disorders
(Traits)
• Autosomal dominant
• Autosomal recessive
• X-linked (dominant or recessive)
• Y-linked
Recessive VS Dominant
1. Autosomal Dominant
1. Autosomal Dominant
1. Autosomal Dominant
2. Autosomal Recessive
X-linked Inheritance
X-linked Dominant
X-linked Recessive
3. Polygenic (Multiple-gene )Diseases
3. Polygenic (Multiple-gene )Diseases
• Disease caused by variants in multiple genes
• DM
• CHD
• HTN
Multifactorial (Complex)Diseases
Thank you