Mutations may occur at the gene level or at the chromosome level.  They may occur at a single gene location or at multiple locations.  Mutations that occur at the gene-level may involve a single gene (e.g., sickle cell anemia, early onset Alzheimer’s disease) or multiple genes across multiple chromosomes.  Most single gene mutations are benign and cause no ill effects.  They are naturally occurring variations that cause no change in function and serve as the basis of genetic diversity both within groups and across populations.  Unlike gene mutations, most chromosome-level mutations are harmful, and some may be lethal.  Down syndrome is one example of a chromosome level mutation (an extra chromosome 21) that causes disabilities.

Genetic Variability

It is not uncommon for one member of a gene pair (considered dominant) to have greater influence on function than the other gene (considered recessive).  If both genes are identical, which is customary, then it doesn’t matter which gene is dominant.  The functionality is supported by either gene.  If one gene is different, however, then dominance matters a great deal.  Whichever gene is dominant will be invoked (expressed).  It is important to remember that differences between the two genes in a pair are common, and these differences may or may not lead to a change in function or to disease.

Ova and sperm are unique.  Unlike all other cells in the body, they possess only a single set of chromosomes (a total of 23 in each). Thus, they do not have any paired genes.  Once an ovum is fertilized by a sperm, then the resulting fertilized egg will possess the normal complement of 23 pairs of chromosomes with paired genes (one set from each parent).  The questions then are: what genes were passed on from each parent, which (if any) could lead to disease (a harmful mutation), and how are they paired up.  A family medical history mapped in a pedigree may help answer some of these questions (see Part 1 – Genetic Heritage available at

The BRCA Genes

Several genes have been identified that influence the growth and development of cells, including cancer cells.  Most of these genes are responsible for suppressing changes in cells that lead to cancer.  Genetic mutations that result in the loss of this functionality are the cause of most cancers.  Acquired (not inherited) genetic mutations occur during life and are often caused by environmental factors (e.g., ultraviolet radiation), life-style (e.g., smoking), disease (e.g., hepatitis C), and numerous other factors.  The cause (etiology) of sporadic or acquired cases is often unknown. One example is mutation of the HER2 gene which accounts for ~15-20% of acquired breast cancers.

Inherited (germ-line) mutations can be passed from parent to child.  A wide variety of mutations in one or both of the BRCA1/BRCA2 genes leads to a significant number of hereditary breast and ovarian cancers.  Collectively, they account for ~20%-25% of breast and ~15% of ovarian cancers.  A synopsis of the role of genetics in cancer is available at (

If you have a BRCA gene mutation, it is important to know that it puts you at risk for developing certain types of cancer.  It does not mean that you will develop cancer.  Even within the same family, there may be considerable variability in whether or not the mutated gene will lead to cancer.  There may be other factors including genetic (e.g., whether one or both genes in the pair are mutated), reproductive (e.g., history of pregnancy/ breast feeding), and/or environmental (e.g., smoking, alcohol) which influence whether or not the mutated BRCA gene will be expressed and cancer will develop.

Women whose family medical history indicates they are at high risk for developing breast or ovarian cancer are eligible for genetic counseling and screening for the BRCA1/BRCA2 gene mutations.  Genetic counseling prior to testing is strongly recommended.  This provides an opportunity for risk assessment based on personal and family history, an understanding of the potential advantages and disadvantages of genetic testing, and assessing the risks that children may or may not have inherited the gene.  Additional information about BRCA gene mutations and screening for them is available from the National Cancer Institute (

Breast Cancer Screening

October 2019 is Breast Cancer Awareness Month.  Women who have close family members – mother, sisters, and daughters – with breast cancer have a higher risk for developing it.  Consult with your healthcare provider regarding recommendations for screening.  Modalities for screening have advanced in recent years.  These include digital mammography, sonography, magnetic resonance imaging, and genetic screening for BRCA1/BRCA2 mutations.


Jorde, L.B.  (2014).   Genes and genetic diseases (Chapter 4) and Genes environment-lifestyle, and common diseases (Chapter 5).  In: K. L. McCance, S. E. Huether, V. L.  Brashers, V.L., and N. S. Rote, Pathophysiology:  The Biologic Basis for Disease in Adults and Children (7th ed.), St. Louis:  Mosby/Elsevier.

McCance, L. and Huether, S. (2014) Pathophysiology: The Biologic Basis for Disease in Adults and Children. (7th ed.).  St. Louis: Mosby.

National Cancer Institute.  (2015.)  BRCA1 and BRCA2:  Cancer Risk and Genetic Testing.

Serjeant, G. R. (2013.)  Natural history of sickle cell disease. Cold Spring Harb Perspect Med, 3(10):a011783. doi: 10.1101/cshperspect.a01178.

National Library of Medicine, Genetics Home Reference, Bethesda, MD. Illustration:

Peventative Services Task Force. (2016.)  Final Recommendation Statement.  Breast Cancer: Screening.  May 2019. RecommendationStatementFinal/breast-cancer-screening1.

Zhang, X., et al. (2014.)  BMC Cancer, 14(625), doi: 10.1186/1471-2407-14-625.

Zou, Z., Liu, C., Che, C., Huang, H.  (2014.) Clinical genetics of Alzheimer’s disease.  Biomed Res Internat’l,  2014:291862. doi: 10.1155/2014/291862.