Chapter 22: Medical Genetics and Cancer

What are the four common patterns of inheritance?

1. Autosomal recessive

2. Autosomal dominant

3. X-linked recessive

4. X-linked dominant

What is Genome-Wide-Association-Studies (GWAS)?

• An approach to identify genetic variation that causes or contributes to human diseases is by analyzing human genome sequences directly

• GWAS is the examination of a genome-wide set of genetic variants among different individuals to see if any variant is associated with a disease or other trait

• Usually tries to find an association between one or more single nucleotide polymorphisms (SNPs) and a disease or other trait

Manhattan plot

A graph for genes on chromosomes resembling a city, hence “Manhattan”

Village plot

A smaller Manhattan plot, also graphing genes on chromosomes, for a smaller group of results

Genetic Testing vs Genetic Screening

• Genetic testing refers to the use of tests to discover if an individual has a genetic abnormality

• Genetic screening refers to population-wide genetic testing

What are the two types of genetic testing before birth?

Noninvasive Prenatal Testing

• Analyze the cell-free DNA (cfDNA) present in the blood of the pregnant mother

• cfDNA is usually identical to the DNA of the fetus

• Can be conducted as early as week 10 of pregnancy

Amniocentesis

• Fetal cells are obtained from the amniotic fluid

• Grown for 1-2 weeks to increase cell numbers

• Karyotyping performed on cells to observe chromosome number and structure

What is the Genetic Basis of Cancer?

Cancer is a disease characterized by uncontrolled cell division

• It is a genetic disease at the cellular level

• Human cancers are classified according to the type of cell that has become cancerous

  • More than 100 kinds have been identified

What are the three characteristics of Cancer?

1. Most cancers originate from a single cell

• A growth is clonal in origin

• A cancer cell divides to produce two cancer cells

2. Cancer is a multistep process

• Begins as a precancerous benign growth (not invasive)

• Additional genetic changes lead to cancerous growth

3. Cancer growth is malignant

• Invasive cancer cells invade surrounding healthy tissues

• Metastatic – Moves to a different site in body and causes secondary tumors

Oncogenes vs Tumor Suppressor Genes

Genes that are involved in cancers are classified as

• Oncogenes

  • Mutant gene that is overexpressed and overactive

  • Contributes to cancerous growth

  • Most of oncogenes result from Growth Factor genes (e.g., Epidermal growth factor)

• Tumor suppressor genes

  • Gene that prevents cancers

  • Loss-of-function in a tumor-suppressor gene can allow cancerous growth to occur

What are the four types of mutation that can change a proto-oncogene into an oncogene?

1. Missense mutation

2. Gene amplification (i.e. duplication)

3. Chromosomal translocation

4. Viral integration

What are the characteristics of Tumor Suppressor Genes?

Tumor suppressor genes prevent cancerous growth

• When tumor suppressor genes are mutated that leads to inactivation, cancer is more likely to occur

• Both copies of a tumor-suppressor gene need to be inactivated to promote cancerous growth

What are the two ways that the function of Tumor-Suppressor genes can be lost?

1. A mutation in the tumor-suppressor gene itself

• The promoter could be inactivated

• An early stop codon could be introduced in the coding sequence

2. Aneuploidy

• Chromosome loss may contribute to the progression of cancer if the lost chromosome carries one or more tumor-suppressor genes

How do epigenetic changes contribute to cancer and other diseases?

Several types of chromatin modifications are found to be abnormal in cancer cells:

• DNA methylation

• Covalent modification of histones

• Chromatin remodeling