Genetic Disorders

Genetic Disorders

Health problems caused by one or more abnormalities in the genome; typically a mutation in a single gene or abnormal chromosome number

Mendelian (Monogenic) Disorder

A genetic disorder caused by a mutation in a single gene

Most traits and disorders are influenced by

Multiple genes, environment, behavior, microbiome, lifetime interactions, and random variation

Genome

All the DNA contained in an organism’s cells

Gene

A sequence of DNA that codes for a specific protein

What does DNA do?

Encodes instructions to build RNA molecules and proteins

Central Dogma of Biology

DNA → RNA → Protein

Cystic Fibrosis (CF)

A genetic disorder that causes problems with breathing and digestion

Cause of Cystic Fibrosis

Mutation in the CFTR (cystic fibrosis transmembrane conductance regulator) gene

Inheritance of Cystic Fibrosis

Autosomal recessive; requires two abnormal copies of the gene

Number of CFTR mutations

Many mutations exist; most common is deletion of a single amino acid

Effect of common CF mutation

Produces a CFTR protein with abnormal structure that cannot function properly

CFTR protein function

Transfers chloride ions out of cells

Primary effect in lungs (CF)

Failure to transport chloride ions leads to thick mucus buildup

Why CF patients get infections

Excess mucus in lungs makes them highly susceptible to infections and chronic lung damage

Sickle Cell Anemia

A genetic disorder that affects the shape and health of red blood cells

Cause of Sickle Cell Anemia

Mutation in hemoglobin, specifically the beta-globin gene

Inheritance of Sickle Cell Anemia

Autosomal recessive; requires two abnormal copies

Specific mutation in Sickle Cell

Single nucleotide change causes valine to replace glutamate in hemoglobin

Effect on hemoglobin

Abnormal hemoglobin structure forms

Effect on red blood cells

Cells become sickle-shaped instead of round

Problems with sickle-shaped RBCs

More likely to clot and are destroyed prematurely

Result of RBC destruction

Reduced number of circulating red blood cells (anemia)

Aneuploidy

A condition where an individual has an abnormal number of chromosomes

Normal human chromosome number

46 chromosomes

Trisomy

Presence of one extra chromosome

Monosomy

Presence of one missing chromosome

Outcome of most aneuploidies

Not compatible with life; development often stops early after fertilization

Down Syndrome

A chromosomal disorder caused by trisomy 21 (extra chromosome 21)

Cause of Down Syndrome

An individual has three copies of chromosome 21

Gene expression in Down Syndrome

Genes on chromosome 21 are overexpressed

Effects of Down Syndrome

Physical growth delays, varying degrees of intellectual disability, and characteristic facial features