Genetics and Age-Related Macular Degeneration

Information for this article provided by Asper Ophthalmics

What is DNA?
DNA (deoxyribonucleic acid) is a molecule that contains all of the genetic instructions needed to develop and maintain an organism. It is a long structure resembling a winding staircase. Each step of the staircase consists of two building blocks called nucleotides. There are four nucleotides: A (adenine), T (thymine), G (guanine), and C (cytosine). They always form the same pairs in the steps of the DNA staircase: A with T, and C with G. Human DNA comprises nearly three billion (3,000,000,000) nucleotides arranged in a specific order. The order in which the nucleotides occur determines the information conveyed.

DNA resides in the nucleus of each cell and carries the complete set of instructions for making all of the proteins a cell needs to function properly. Each type of cell uses only a part of the genetic information stored in DNA. Genetic material in DNA is responsible for all of the traits that are passed on from one generation to the next.

A gene is a region of DNA containing a particular set of instructions that enables a cell to produce a protein. While the DNA provides instructions, proteins are the molecules responsible for nearly all aspects of cellular activity. Humans have approximately 20,000 – 25,000 genes. The complete set of genes is called a genome. Every person has two copies of each gene: one inherited from the mother and one from the father.

When Genes Go Rogue
Sometimes, for any number of reasons, one or both genes in the pair becomes altered. This can cause unexpected abnormalities in the body. Not all abnormalities are bad, but they can cause problems like disease and physical insufficiency.

Different versions of the same gene are called Alleles. Alleles can be present in one of two states: homozygous (when alleles inherited from the father and from the mother are similar) or heterozygous (when alleles inherited from the father and from the mother are different). An allele can be dominant (encodes a protein in the heterozygous state) or recessive (encodes a protein only in the homozygous state).

Alleles arise from either mutations or SNPs (single nucleotide polymorphisms, aka “snips”). Mutations are rare changes in the DNA sequence, affecting less than 1% of the population. SNPs are gene pairings where one of the two copies contains an altered nucleotide. Alleles caused by SNPs are more frequent than alleles caused by mutations.

Mutations and SNPs can be harmful if they destroy the DNA sequence needed for encoding a functional protein. The functioning of a cell (and also the entire body) depends on a continuous interplay of thousands of proteins acting together in just the right amounts and in just the right places. If no protein or a non-functional protein is encoded due to a mutation or SNP, the activity of a cell can be disturbed. This can lead to the development of a disease, or it can result in an inability to metabolize or break down drugs normally.

Many diseases have their roots in our genes. Increasingly more evidence is being found regarding the associations of certain changes in DNA with different disorders. Common disorders such as diabetes, heart disease, and most cancers are caused by the complex interaction between multiple genes and environmental factors.

Genetic Testing
Genetic testing involves examining a patient’s DNA for mutations or SNPs linked to an inherited disease or disorder. The results of a genetic test can confirm or rule out a suspected genetic condition or help determine a person’s chance of developing a genetic disorder in the future.

Genetic testing serves several purposes:

  • Confirming the diagnosis of a symptomatic individual
  • Testing for genetic diseases in adults before they cause symptoms
  • Carrier screening. A carrier is a person who carries one copy of a gene for a disease that requires two copies for the disease to be expressed. A carrier is not affected by the disease.
  • Finding out if a person carries a genetic marker of the disease and may pass it on to offspring
  • Finding possible genetic diseases in unborn babies
  • Screening embryos for disease
  • Helping, in some instances, to choose the most effective drug and its optimal dose for a patient

Genetic tests also allow families to avoid having children with very severe and devastating genetic diseases, or to identify people at high risk for conditions that may be preventable. Genetic testing has been performed for several years, and it has already helped improve medical health care.

The Genetics of Age-related Macular Degeneration (AMD)
Susceptibility to AMD is a multi-factorial trait involving both genetic and environmental factors. Several genes have now been associated with the development of AMD.

The best available markers of AMD risk are SNPs at chromosomes identified by the codes 1q31-32 and 10q26. SNPs in the genes labeled complement factor H (CFH) and LOC387715 (aka ARMS2) have been found to be responsible for a substantial fraction of AMD risk. Evaluation of these two genes permits identification of individuals at high risk of developing the disease. It also provides supportive information for genetic counseling and helps to confirm the diagnosis.

Early detection and diagnosis of AMD is important to delay progression of disease. Besides genetics, there are modifiable risk factors for AMD such as hypermetropy (longsightedness), smoking, high blood pressure, cardiovascular diseases, and unhealthy diet. AMD risk assessment is, therefore, necessary for early diagnosis and for genetic counseling of family members. With prior knowledge of increased risk for developing AMD, patients will better understand the importance of good health habits and regular eye exams.

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Allikmets R, et al. Mutation of the Stargardt Disease Gene (ABCR) in Age-Related Macular Degeneration. Science 1997; 1805-7. [PubMed:9295268]

Kanda A, et al. A variant of mitochondrial protein LOC387715/ARMS2, not HTRA1, is strongly associated with age-related macular degeneration. Proc Natl Acad Sci U S A. 2007 Oct 9;104(41):16227-32. [PubMed: 17884985]

Maller J, George S, Purcell S, et al. Common variation in three genes, including a noncoding variant in CFH, strongly influences risk of age-related macular degeneration. Nat Genet 2006;38:1055–1059.[PubMed: 16936732]

Hageman GS, et al. A common haplotype in the complement regulatory gene factor H (HF1/CFH) predisposes individuals to age-related macular degeneration. Proc Natl Acad Sci U S A. 2005 May 17;102(20):7227-32.[PubMed: 15870199]


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