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Discuss why males are more likely to suffer from colour vision deficiencies, with specific
reference to the genetic mechanisms involved.
The soul, fortunately, has an interpreter often an unconscious but still a faithful interpreter
in the eye. Charlotte Bront, Jane Eyre (1847)
Colour serves as a non-linguistic code that provides important information about the
world around us. However, fully 8% of the male Caucasians (Drummond-Borg, Deeb, &
Motulsky, 1988)either cannot distinguish red from green, or see red and green differently
from most people. This condition is known as colour blindness, and more than 75% of the
affected individuals report struggling with daily tasks that most people take for granted, such
as determining when meat is cooked, or distinguishing traffic lights (Steward & Cole, 1989).
Colour blindness also excludes people from numerous professions such as police officers, fire
fighters, and public transit drivers, and causes visual miscommunication for children in
schools, since colour cues are used to teach, for example, reading and mathematics.
Red-green colour blindness is the most common form of colour blindness, but it
affects only 0.5% of women (Drummond-Borg et al., 1988). The main cause of the difference
in percentage of affected males and females is X-chromosome linkage (Wilson, 1911, cited in
Deeb et al., 1992). The essay focuses on explaining the genetic mechanism that makes males
more likely to suffer from colour vision deficiencies. First, it will clarify how colours are
perceived in healthy human individuals, using then existent literature to classify colour
blindness into categories. It will subsequently explore the inheritance patterns of red-green
colour blindness, and also explain the rearrangements undergoing at the genomic level that
cause defective colour vision. Recent advances in gene therapy that might help cure the
disease are also discussed. This essay will also outline key areas where unsolved questions
remain, before summarising key points that explain the disproportion in the expression of
colour vision deficiencies in the population.

Colour vision
Colour vision depends on the ability of cone-cells to discriminate among different
wavelengths of light. In healthy human individuals, there are three types of cone
photoreceptors in the retina. They contain different photopigments, known as opsins, that are
sensitive to either short-(S), middle-(M), or long-wavelenghts (L). The S, M, and L
photopigments have overlapping spectra with peaks at 426, 530, and 563 nm, for the blue,
green, and red pigments, respectively (Merbs & Nathans, 1992). Any stimulus in the visible
spectrum of a particular wavelength can be matched by comparing absorbtions in these three
pigments according to Young-Helmoltz theory (Young, 1802, cited in Wissinger & Sharpe,
1998). Because three pigments are required to match all others, humans and other primates
are known as trichromatic (Surridge, Osorio, & Mundy, 2003; Jacobs, 1993), and colour
discrimination depends on the correct overlap between the spectra of cones.
Types of inherited colour defects
Inherited colour vision defects are known for the blue, green, and red colour vision
(Pokorny, Smith, Verriest, & Pinckers, 1979). Whereas congenital defects for the blue colour
vision affect only 1 in 100,000 individuals, defects for red and blue are common, affecting
8% of the male Caucasians (Drummond-Borg et al., 1988). Red-green colour vision defects
can be divided into four subclasses based on the severity and the type of cone photoreceptor
missing (Deeb, 2004). Anomalous trichromats have three pigments, but their red (in the case
of protanomalous trichromacy) and green (in the case of deuteranomalous trichromacy)
pigment absorbtion does not accept the proportions that satisfy healthy subjects in colour
vision tests (Pokorny et al., 1979). This means that they will accept colour matches that a
normal will not. Dichromats lack completely either red pigment sensitivity (protanopes), or
green pigment sensitivity (deuteranopes), using only two primary colours to match all others.
Inheritance patterns
The cause of the higher incidents of red-green colour blindness in males than in
females was established on the basis of examinations of pedigrees and genetic analyses

(Kalmus, 1965; Jaeger, 1970). The genes for green and red were found on the X
chromosome - at Xq28 (Vollrath , Nathans, & Davis, 1988). This means that when the Xq28
gene gets faulty, red-green colour blindness follows the pattern of inheritance known as Xlinked recessive inheritance (Wissinger & Sharpe, 1998). Women have two copies of the X
chromosome (XX). If one gene copy is faulty, and there is a back-up working gene on the
partner X chromosome copy, she will not be affected by the condition (Deeb, 2004). Women
who are carriers of a faulty gene at Xq28 will have some cells in their body in which the
faulty gene is activated and others in which the working copy of the gene will be activated.
The faulty gene will not be expressed because there will be enough cells to produce the
necessary protein with the working copy of the gene. Therefore, she will have normal colour
vision, but will carry an inactive defective allele that will be transmitted to half of her sons
and none of her daughters if the father has normal colour vision (Neitz & Neitz, 2000).
Women are affected only in the rare case when both copies of the X chromosome are faulty.
Men have an X and a Y chromosome (XY). Because they have only one copy of the X
chromosome and no other X chromosome to provide back-up, the faulty gene is expressed
in the phenotype, so they will inherit the condition. To express colour blindness the genotype
must be XX with two defective alleles or XY with a defective allele on the X chromosome.
In this way, red-green colour blindness is inherited as X-chromosome linked recessive trait,
consequently being expressed in more male than female individuals.
However, some female carriers were found to exhibit a mild version of the deficiency
exhibited by their sons, or even full colour deficiency, but in rare cases (Verriest, 1972, cited
in Jordan & Mollon, 1993). This anomalous trichromacy in female carriers is usually
explained by X-chromosome inactivation (i.e., lyonization), a process ensuring that males
and females have the same number of active X chromosomes instructing the body to grow,
develop and function by inactivating most of the genes on the partner chromosome (Lyon,
1961, 1972). During early embryonic development, a parental X chromosome is randomly

inactivated in any given cell, and all the descendants of that cell have this inactivation. Due to
this process, the carriers are functionally hemyzigous in all their somatic cells, meaning that
their retina consists of a mosaic of cells expressing the normal and the abnormal X
chromosome at the colour vision loci, as shown by psychophysical evidence (Jordan &
Mollon, 1993). This random inactivation suggests that there is a possibility, contrary to
Mendels laws, for female carriers to have abnormal colour vision expressed in their
phenotype. Because this random inactivation in female carriers cannot be predicted according
to present knowledge and because the findings of Jordan an Mollon (1993) suggest that there
might be more cases of females with colour vision problems Mendels laws predict, future
research should investigate more carefully the process of random inactivation. Still, such
cases are thought to be rare, so the problem of colour vision deficiencies remains a problem
that is mostly faced by men.
Molecular genetic basis of red-green colour blindness
The molecular nature basis of colour vision deficiencies was first delineated by
Nathans and colleagues (1986), who cloned and sequenced the genes encoding the red and
green visual pigments. The surprising finding was that there are individual variations in the
number of red/green colour genes, being supported by recent findings (e.g., Nathans et al.,
1992). They showed that colour-blind individuals have deletions of green pigment genes,
duplications of red or green genes, or fusion genes consisting of portions of red- and greenpigment genes. They concluded that the condition results from a process called unequal
homologous recombination. X-chromosomes for the red and green photopigments are
homologous, with 96% identity at the amino-acid level, and also lie close together in the
tandem array. Because of the proximity and the high homology, during meiosis a pair of
chromosomes can join by crossing over in the region encoding for red and green pigments,
and then break between the two genes of a chromosome, or within a gene (Sharpe, Stockman,
Jgle, & Nathans, 1999). This results in deletion of green pigment genes or duplications of

red or green genes. Breaking between a gene produces a hybrid gene composed part of a
green pigment gene and a part of a red pigment gene. The hybrid gene produces
nonfunctional pigments similar to the normal ones, which leads to dicromatism, or pigments
with spectral sensitivities intermediate between those of red and green pigments, which leads
to anomalous trichromacy.
It is important to note that the great similarity between red-green photopigment genes
means that a small number of changes in the sequence is enough to account for changes in the
absorption spectra of the red and green pigments. So there is a variety of hybrid genes that
can be generated by slight changes, depending on the breakpoints. For example, Neitz, Neitz,
and Jacobs (1989) examined a fusion gene that produces deuteranopia, and found that it
resulted from intergenic recombination between the region downstream of the first gene in
one array and the region downstream of all genes in the second array producing an array with
a single L pigment gene.
Gene therapy
The possibility of curing colour blindness using gene therapy was investigated using
adult New Word primates such as the squirrel monkey (Saimiri sciureus) which were born
colour-blind (e.g., Mancuso et al, 2009). Squirrel monkeys offer an analogue model for
human colour vision due to the sex linked variation: While female can have either
dichromatic or trichromatic vision, all males are red-green colour-blind (Jacobs, 1993). This
is because they have a single, polymorphic locus on the X chromosome with three allelic
versions of the opsin gene that specify one of the possible M/L photopigments (Jacobs,
1993): Females which are trichromatic at the locus are trichromatic, whereas homozygous
females and all males are dichromatic (Bunce et al., 2011). Conceptually, to induce
trichromatic vision into homozygous females, it is necessary to identify the appropriate DNA
sequence and cell types, then to develop a suitable way to get DNA into these cells (Mancuso
et al, 2009). For example, Mancuso and colleagues (2009) showed that adding a third type of
cone pigment to dichromatic retinas of adult monkeys missing L pigment gene can produce

trichromatic vision behaviour .They injected a virus carrying a gene for the missing
photopigment into the retina of adult protanotrope squirrel monkeys. Twenty weeks after
injection the new pigment was expressed in cone photoreceptors and the formerly
dichromatic monkeys began to discriminate between two colours which had looked identical
to them since birth. In addition, the cone pigment does not require administration at a very
young age, so there is no need of major neural rewiring like that seen during retinal
development. Still, they fail to establish how the sensation is internally perceived, as one of
the questions arising from these results is what type of cone-opponent ganglion is active in
the treated monkeys (Shapley, 2009). The success of gene experiments on inducing
trichromatic vision in dichromatic New World Primates offer promise for the potential of
gene therapy to cure adult vision disorders.
Conclusion
Red-green colour- blindness is an inherited condition that affects mainly the male
population (Deeb, 2004). Research reviewed in this essay illustrates how sex differences
account for differences in the expression of red-green colour blindness: The faulty gene that
causes red-green colour blindness is similarly inherited by males and females, but expressed
considerably more frequently in males because it is X-linked. Although no cure is known as
yet, animal models have demonstrated amelioration following the gene therapy, which
suggests that gene therapy can possibly correct colour vision deficiencies in humans.
However, whilst red-green colour blindness has been studied for over half a century,
yet several unresolved questions remain. For example, how exactly is trichromatic vision
perceived differently from dichromatic vision in animal models which had their dichromacy
corrected. By analogy to squirrel monkeys which have been studied as a stand-in model for
colour vision deficiencies resulted from direct translation of genetic information, one agenda
in future research should be to investigate how and the extent to which gene therapy can
influence the X-chromosome inactivation in women who are anomalous for heterozygous

trichromacy using squirrel monkeys. In spite of these, research reviewed in this essay is clear
with respect to the genetic mechanism that makes males more likely than females to suffer
from colour blindness.

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