Genetics of Color Blindness

Introduction

The inability to see the differences between some colors can be categorized as color blindness. Colorblind is a term used to describe this condition. But in rare cases, everything is seen in shades of black and white, called actual color blindness. A group of vision disorders is responsible for these vision deficiencies. It is related to mutation (the changing of the structure of the gene, resulting in variations) in the gene. The transformation mainly occurs in between the various components of retinal cones (responsible for color vision). L-cones, M-cones, and S-cones are three various cone photopigments on which human color vision depends. Inability to see some shades of red and green are the most common color deficiency. This article shows the interplay of genes in color blindness.

What Is Color Blindness?

Color blindness is an inability to see the differences between certain colors. The most common colors are red and green. Color vision deficiency (CVD) is a disease that affects the retina (part of the eyes present at the back side of the eyes), leading to altered color perception. Three cones, namely L-cones, M-cones, and S-cones, are responsible for color vision (trichromatic) in humans. L-cones and M-cones are coded by two opsin genes. The photopigments have wavelengths such as long-wavelength cones (557 nm; red), middle-wavelength cones (530 nm; green), and short-wavelength cones (426 nm; blue), respectively. Color blindness affects 0.5 to 8 % of the general population and is of various types.

The following are the types of color pigments:

• Protanopia - When L-cones are affected, the deficiency is called protanopia.

• Deuteranopia - The condition in which there is the loss of M-cones.

• Tritanopia - The condition in which there is the loss of S-cones.

The following are the types of color blindness:

• Red-Green Color Blindness - It is the most common type of congenital (present at the time of birth) color vision deficiency. It is caused by both protanopia and deuteranopia. It is an X-linked recessive disorder, affecting 0.35 % of female new births and 5 % of male new births.

• Yellow-Blue Color Blindness - It is caused by tritanopia. This disorder is believed to be acquired rather than congenital, appearing later in life in association with other eye conditions that seem to affect the S-cones, such as glaucoma (an eye disease in which patients suffer from swollen eyes and vision problems).

• Achromatopsia - It is a genetic disease that occurs due to all three types of cones, affecting one in 30,000 live births in the general population. Patients typically present with signs and symptoms of decreased visual acuity, photophobia, nystagmus, and, most importantly, loss of color perception. Affected individuals depend mainly on rods during the night and daytime vision. Rods are light-sensitive photoreceptors; in bright-light conditions, rods are not highly efficient, leading to the development of the symptoms of achromatopsia.

What Causes Color Blindness?

Various genes are responsible for color blindness in humans. Some of them are OPNILW (opsin 1 long wave), OPN1MW, ATF6 (activating transcription factor 6), CNGA3 (cyclic nucleotide-gated channel subunit), CNGB3, GNAT2 (guanine nucleotide-binding protein), subunit alpha-2, PDE6H (phosphodiesterase 6H), cone-specific inhibitor, and PDE6C.

Some other causes are explained as follows:

• Inherited Disorder - It can be mild, moderate, or severe inherited.

• Diseases - Diabetes (a disorder in which the body has high sugar), glaucoma(a group of eye conditions that damage optic nerve), Alzheimer's disease(a brain disorder that slowly destroys memory and thinking skills), sickle cell anemia(blood disorder where blood cells become sickle/crescent shaped) are some conditions that cause color blindness.

• Certain Medications - The drugs which can treat certain autoimmune diseases, heart problems, and hypertension can alter color vision.

• Aging - The ability to see colors are reduced slowly as age progresses.

• Chemicals - Chemicals such as carbon disulfide and some fertilizers may cause loss of color vision.

How Are Genes Related to Color Blindness?

Complete color blindness can lead to severe blindness and symptoms such as photophobia (fear of the light) for refractive errors ranging between myopia and high hyperopia. Color blindness is more prevalent. The functioning of cones or rods present in the eye may affect the functioning of the eye. Complete achromatopsia can have visual equity as low as 20/200. Mutation (alteration in the structure of the gene) in the following gene causes color blindness:

• Transcription factor 6 (ATF6).

• Cyclic nucleotide-gated channel subunit alpha 3 (CNGA3).

• Cyclic nucleotide-gated channel subunit Beta 3 (CNGB3).

• Guanine nucleotide-binding protein G(t).

• Subunit alpha-2 (GNAT2).

• Phosphodiesterase 6H (PDE6H).

• Phosphodiesterase 6C (PDE6C).

GWAS shows that many genes are involved in color blindness. This research enlightened the gene therapy for treating various diseases. Gene therapy aims to alter the expression of human genomes to treat inherited diseases, cancer, and infectious diseases.

Gene therapy can be applied through many processes:

• Silencing a Dysfunctional Gene - In this step, adding a new or modified gene to cure a disease, and overriding a harmful gene with a correct, healthy gene copy helps in deactivating the dysfunctional gene. This is done using human gene editing technology, plasmid deoxyribonucleotide acid (DNA), viral vectors, bacterial vectors, or patient-derived cellular gene therapy products.

• Vector - Vector refers to organisms that transfer the functional gene to the human or plant body. Vector delivery is one of the main types of delivery products used in ophthalmology, especially in retinal gene therapy. This could be administered by injecting the viral vector into the subretinal cavity, where vectors are delivered to the target cells. The virus infects retinal pigment epithelial cells (RPE cells), where it gets translated into the corresponding protein products. In addition, the vector can be administered intravitreally.

• Mutation - CNGA3 mutations are the most common cause of achromatopsia in the Middle East and China, accounting for around 60 % of the cases. Several animal models were created to study the characteristics of this gene. The first described model was Cnga3 knockout mice, which showed that mutations in CNGA3 led to the progressive death of cones and subsequent loss of cone-mediated light response. Induced mutations in the CNGA3 gene in sheep models were observed to diminish the physiologic function of the cone. These help in restoring the function of rods and cones present in the eye.

Conclusion

Complete color blindness leads to photophobia and severe blindness. Color blindness is caused by many reasons but in context of gene OPNILW (opsin 1 long wave), OPN1MW, ATF6 (activating transcription factor 6), CNGA3 (cyclic nucleotide-gated channel subunit), CNGB3, and GNAT2 are responsible for color blindness. Gene therapy is a promising novel therapy for the deficiency of color vision. There is improvement in cone cell functions based on many studies, experiments, and clinical trials. There is a need for more understanding of the genetics of color blindness.