Indian Journal of Ophthalmology

: 2000  |  Volume : 48  |  Issue : 1  |  Page : 5--13

Molecular genetics of cataract.

C Kannabiran, D Balasubramanian 
 L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad-500 034, India

Correspondence Address:
C Kannabiran
L.V. Prasad Eye Institute, L.V. Prasad Marg, Banjara Hills, Hyderabad-500 034


Studies on hereditary congenital cataracts have led to the identification of genes involved in formation of these cataracts. Knowledge of the structure and function of a particular gene and the effect of disease-associated mutations on its function are providing insights into the mechanisms of cataract. Identification of the disease gene requires both the relevant clinical data as well as genetic data on the entire pedigree in which the disease is found to occur. Genes for hereditary cataract have been mapped by genetic linkage analysis, in which one examines the inheritance pattern of DNA markers throughout the genome in all individuals of the pedigree, and compares those with the inheritance of the disease. Cosegregation of a set of markers with disease implies that the disease gene is present at the same chromosomal location as those markers. The genes so far identified for hereditary cataracts in both humans and animal models encode structural lens proteins, gap junction proteins, membrane proteins and regulatory proteins involved in lens development. Understanding of the mechanisms of hereditary cataract may also help us understand the manner in which environmental and nutritional factors act on the lens to promote opacification.

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Kannabiran C, Balasubramanian D. Molecular genetics of cataract. Indian J Ophthalmol 2000;48:5-13

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Cataractogenesis essentially involves disruption of the ordered structure of the lens. It is brought about by either quantitative or qualitative alterations in lens components such as macromolecules, small molecules (water and metabolites) or the cells themselves. Although knowledge of cataract itself, as well as its remedy is centuries old, understanding of its pathogenesis has been possible only within the last century. Insight into the basis for lens transparency came initially from biochemical and biophysical studies of the lens, followed by molecular genetic approaches during the later part of this century, which were aimed at identifying the genetic defect in hereditary cataracts. This review attempts to provide a glimpse of the genetic bases for hereditary cataracts, and highlight how these studies are contributing to an understanding of possible pathways leading to cataract formation.

 The Lens

The vertebrate eye lens has remained a challenge for structural and evolutionary biologists since it represents a biological system that functions as an optical device, with the added property of being elastic. The functions of the lens are supported by a simple architecture that is based on a single type of cell and a very high concentration of intracellular protein. The human lens is derived from the surface ectoderm, which thickens to form the lens placode and then invaginates to form the lens pit. The lens pit closes to form the lens vesicle from the posterior side of which primary fibre cells are formed. The lens cavity is filled by the elongating primary fibers. This process takes place in humans between the fourth and sixth weeks of gestation. The process of formation of secondary fibre cells begins thereafter and continues throughout life. Anterior epithelial cells divide to form the secondary fibre cells at the lens equator where they elongate both anteriorly and posteriorly to surround the earlier fibre cells in onion-like layers. Terminal differentiation of the fibre cells involves loss of all organelles resulting in cells without nuclei and mitochondria at the centre of the lens. The initial stages of nuclear breakdown are said to resemble the process of apoptosis.[1,2] The lens is surrounded by a capsule, which is produced anteriorly by the epithelium and posteriorly by the fibre cells.[3] The proteins comprising the capsule are collagen, laminin, entactin, heparin sulfate proteoglycan and fibronectin.[3]

The proteins constitute about 30-35% of the entire mass of the lens being present at concentrations above 450 mg/ml and therefore capable of packing at very high densities. Due to the loss of nuclei and other organelles these proteins do not turn over and are present throughout life. The lens maintains a gradient of refractive index from the center to the periphery.[3] This correlates with the difference in water (and protein) content of the cortex (80% water) versus the nucleus (68% water). This protein gradient is accompanied by a constant osmotic pressure throughout the lens. It transmits efficiently over the entire range of visible light and beyond it till about 1200nm but transmits very little below 300nm. In addition, dilution of proteins below 450 mg/ml results in increased light scattering. Loss of transparency occurs as a result of ageing, partly due to the cumulative effect of alterations in lens proteins in response to light or oxidizing agents[4] and partly due to age-related changes in the cytoskeleton and cell membranes.

 Major Structural Proteins of the Lens

The crystallin family of proteins deserves particular mention not only because crystallins are the major structural proteins of the lens, constituting about 80-90% of lens soluble protein, but also because a number of recent studies have disclosed the involvement of crystallins in human hereditary cataracts. They consist of soluble cytoplasmic proteins; the dense yet highly ordered arrangement is essential for transparency and refraction by the lens. Morner first described the crystallins in 1893.[5] He fractionated bovine lens crystallins into three soluble and one insoluble fraction. The soluble fractions containedα βand γ crystallins which arc found in all vertebrate lenses. The various human crystallin proteins and their genes are summarized in [Table:1].

The α-crystallins make up 40% of human lens crystallin and consist of two related proteins, αA and βB-crystallin, encoded by separate genes. Although both proteins are expressed at very high levels in the lens, αA-crystalin is essentially a lens-specific protein, being expressed at very low levels in the spleen.[6] On the other hand, βB-crystallin is expressed ubiquitously and is found in high levels in the brain, muscle, lung, thymus, kidney and a number of cell-lines. The α-crystallin in the eye lens exists as a large complex composed of αA and βB subunits. The complex has a molecular mass of 800-1000 kDa. The molecular mass of individual subunits is of about 20kDa. Thus, the native form of α-crystallin is a large complex made up of oligomers of αA and βB-crystallins, arranged so as to confer maximum stability and solubility to the complex (reviewed by Graw[1]). Apart from being a structural component of the lens, the α-crystallin has a distinct protective role in maintaining solubility of intracellular lens proteins and promoting resistance of cells to stress.

The α-crystallins bear sequence homology to the heat shock proteins of Drosophila.[7] αA-crystallin shows sequence homology with heat shock proteins from mouse (sHSP25) and human (sHSP27), and mediates the cellular response to various types of stress such as thermal and oxidative stress. It may even function as a regulator in apoptotic pathways.[1] Apart from these properties, α-crystallin has a more direct role in maintenance of lens transparency by virtue of its ability to mimic the action of a molecular chaperone, as first described by Horwitz.[8] Essentially, α-crystallin executes its chaperone-like function by binding to denatured proteins and keeping them in solution. In the lens, light-induced damage and oxidative or thermal stress effectively bring about loss of transparency through modification of proteins so that they undergo denaturation. α-crystallin binds to a number of proteins, particularly the β- and γ-crystallins, and prevents thermal and photoaggregation.[8,9] Since the lens is susceptible to damage by these agents, and does not possess any mechanism for degradation or extrusion of damaged proteins out of the cells, such chaperone-like activity is crucial in preserving lens transparency

Finally, α-crystallins contribute to cellular architecture by interacting with and regulating the cytoskeleton.[1] Carter et al.[10] found that the beaded filaments, a filamentous polymer seen in lens fibres by electron microscopy, are made up of α-crystallins and cytoskeletal protein.

The β- and γ-crystallins share common structural elements and are therefore regarded as members of a superfamily. The conserved unit of tertiary structure for the β γ- family is the globular domain which is made up of Greek key motifs. Greek key motifs are so called because they resemble a common element in Greek pottery and consist of four-stranded antiparallel β-sheet structures. Two Greek key motifs make up a globular domain [Figure:1].

The β-crystallins consist of two types based on overall charge-they are the acidic (β A1/A3, βA2 and β A4) and basic (βBl, β B2 and β B3) β-crystallins. Each is encoded by a separate gene except for the βA1/A3 which arise from a single gene with two different initiation codons. The native form of β-crystallins consists of oligomers ranging from 40-200 kDa; the largest complexes are probably octamers. They form heterodimers of basic and acidic subunits, as well as homodimers. Formation of dimers apparently requires the linker region between the two domains. The β-crystallins also have non-conserved N- and C-terminal extensions which are absent from the γ-crystallins.

The γ-crystallins exist as monomers of about 20 kDa. Though they possess the conserved structural unit, i.e., the two globular domains, they differ from the β-crystallins in that the linker peptide between the two domains is folded so that the domains interact intramolecularly giving rise to the very compact structure attributed to γ-crystallins. The intramolecular interaction between the globular domains results in their being monomeric. They are found specifically in the lens fibres and are found in very high concentrations in the lens nucleus, which is the hardest, most dehydrated part of the lens. Thus, the γ-crystallin structure is optimal for high-density molecular packing. The γ-crystallin gene cluster includes γA to γF, although polypeptides are found only for γA-D in humans. γE and γF are pseudogenes and are not normally expressed in the human lens.

Other proteins that are important for maintenance of lens architecture are: the a) membrane proteins, which make up 2% of lens protein; b) gap junction proteins, called the connexins, which form gated channels that are required for cell-cell communication; and c) cytoskeletal proteins such as actin, myosin, vimentin, that are common to all tissues, as well as lens specific proteins. Cytoskeletal proteins are responsible for maintaining cell shape during differentiation and may play a role in accommodation.

 Molecular Genetic Approaches

Hereditary cataracts that have been characterized so far show Mendelian inheritance and either result from single-gene mutations or from chromosomal translocations. They can be inherited in an autosomal dominant, recessive or X-Linked mode. Mapping involves establishing the chromosomal location of the disease gene and eventually, identifying the mutation involved. Genetic mapping is done by means of linkage analysis, which involves the use of specific markers whose positions on the chromosome are known relative to each other (see references 11,12,13 for an account of the scope and applications of molecular genetics in ocular disease). These markers are generally polymorphic, i.e., each has many different alleles, and are inherited in a Mendelian fashion. In linkage analysis, one essentially looks at the inheritance of markers at different locations throughout the genome in all members of a pedigree and compares it with that of the disease, to see if the disease is coinherited (or linked) with any set of markers. Coinheritance implies that the disease gene is present at the same chromosomal locus as the linked marker(s). The underlying basis for the assumption of physical proximity of genetically linked markers stems from the phenomenon of crossing over or recombination (exchange of chromosomal material between homologous chromosomes) that occurs during the first stage of meiosis. The closer together two genes are on a chromosome, the less likely they are to recombine. Thus, if the disease locus and the marker locus are close together on the chromosome, they are not likely to be separated by recombination and will show linkage. On the other hand, if the two loci are far apart, recombination is likely to occur between them and they are said to be unlinked.

In order to be able to effectively link the disease gene to a marker locus, one has to be able to unambiguously trace the parental origin of the marker allele. For this, the marker has to be highly polymorphic, i.e., have many different versions in a population so that individuals have a higher chance of being heterozygous for the marker. Earlier mapping studies used protein or antigen markers such as blood group (ABO, Rh, Duffy, haptoglobin, etc.). However, these markers have limited use because protein loci are not sufficiently polymorphic. With the invention of restriction enzymes, these were replaced by the RFLP (restriction fragment length polymorphism) markers. The RFLPs have largely been replaced by microsatellite markers which consist of units of repeat sequences of 2-12 base-pairs. Variability in the number of repeat units in the microsatellites, which can range from one to a few hundreds, gives rise to an enormous scope for polymorphism. With the advent of the Human Genome Project, the human genetic map contains about 6000 microsatellite markers located at closely spaced intervals, thus enhancing the potential to map disease genes accurately.

Genetic mapping by linkage analysis provides the approximate location of the disease gene on a chromosome. Identification of the gene itself can be done in two ways: 1) the region of the genome that was mapped as disease locus is examined for the presence of suitable candidate genes. A candidate gene could be a gene that is specifically expressed in the diseased tissue or has a known or suspected function in that tissue; 2) In the absence of a suitable known candidate in the mapped region, one proceeds by the 'positional cloning' approach, which involves the identification of genes based solely on their position in the genome. In other words, every gene that is located in the given interval is considered as a potential candidate for the disease, and one looks for disease-associated mutations in all genes in the interval. The drawback of this approach is the enormous amount of labor and resources involved. However, the positional cloning approach does not require any assumptions about the nature of the gene product or its function and can lead to new insights into the physiology of a particular tissue or organ. This is because one can identify mutations in a gene whose function is not yet understood; since it is found to be associated with disease, one can infer that it must be required in the normal functioning of the concerned tissue or organ as well.

[TAG:2Hereditary Cataracts

Most of the studies done so far with cataracts of hereditary origin are on families from the Western world, where communities are generally outbred, and hence have a preponderance of dominantly inherited disease. In India, one might expect some proportion of inherited cataracts to be recessive due to widespread consanguinity. In a study conducted in South India, hereditary cataracts accounted for at least one-fifth of all childhood cataracts[14] although the percentage of recessive disease is still an open question. Autosomal dominant cataracts are commonly congenital, and are genetically and morphologically heterogeneous. Clinically similar phenotypes can map to different loci and cataracts produced by the same genotype, as in members of the same family, often show very variable morphologies.

Families with congenital cataract were described as early as 1878,[15] when a Danish physician published a paper entitled 'A cataractous peasant family', wherein he described early-onset cataract in a family of 26 individuals spanning 5 generations of whom 20 individuals were affected by the disease. The pedigree was extended 20 years later, in 1898, when 43 persons were added.[16] It was not until 1949 that this family, which had grown to 542 members in 8 generations, was clinically and genetically studied by Marner,[17] who described the inheritance of the Marner cataract (CAM) as a Mendelian trait having autosomal dominant inheritance with full penetrance. This cataract was mapped[18] to the haptoglobin locus at chromosome 16q22 and re-assessed morphologically by Marner.[16] The cataracts in this family were characterized as "progressive, consisting of fine, dispersed, pulverulent opacities' in the embryonic nucleus with considerable variation between individuals. Outside the embryonic nucleus, zonular or posterior subcapsular opacities were sometimes found. There was considerable variability in the rate of progression with age at surgery ranging from one month to 26 years.[16]

The known loci for autosomal dominant congenital cataracts and corresponding gene mutations, where identified, are summarized in [Table:2].

a.Crystallin genes as the cause of cataract

It is not surprising that mutations in crystallin genes, resulting in proteins with abnormal structure, can result in lens opacity. Maintenance of normal structure as well as normal amounts of various proteins both with respect to monomers and larger multimeric complexes is essential for lens transparency. The overall effect of a mutant structural protein such as a crystallin could conceivably be to perturb the equilibrium with respect to monomers and/or multimers apart from insolubility of the mutant protein itself. The first direct evidence for the association of crystallin genes with cataract came from animal models.[19] [Table:3] lists several examples of hereditary cataracts in mice and their associated gene defects. Cataractous strains of animals such as mouse and guinea pig provide valuable insights into mechanisms of cataract formation since they are easily amenable to genetic and biochemical studies. A notable example is the Philly mouse, a strain with dominantly inherited cataract.[20] The lens of the Philly mouse was found to have an abnormal βB2-crystallin, having an internal deletion of four amino acids.[21]

In humans, a number of recent studies have uncovered the genetic bases for different hereditary cataracts. There are at least five known cataracts that are caused by mutations in crystallin genes. The 'Coppock-like' cataract is a nuclear lamellar cataract (confined to the embryonic nucleus). This cataract was mapped to the γ-crystallin gene cluster on chromosome2.[22] The γE gene in humans is a pseudogene, i.e., it is not normally expressed. It has an inactive promoter and a termination codon in the second exon of the gene; the protein if expressed, would terminate in the first globular domain. In the 'Coppock-like' cataract, mutations in the promoter region of the γE gene result in reactivation of the gene such that the truncated product is expressed at a level that is 10-fold higher than in the normal, being raised to -30% of the γD-crystallin.[23] Incidentally, this is also the first human disease to be associated with reactivation of a pseudogene.

Lift et al.[24] described a pedigree with cerulean blue dot cataract (CCA2) which is associated with a mutation in the βB2-crystallin gene on chromosome 22. Cerulean cataracts have peripheral bluish and white opacifications arranged in layers with occasional central lesions. Although this cataract is congenital, it progressed mildly and lens extraction was performed only in adulthood. This phenotype, which is relatively mild, was conferred by the heterozygous state, which was the case with all affected individuals in the family except one, who was the offspring of affected first cousins and was homozygous for the mutant gene. She presented with microphthalmia and microcornea, underwent cataract surgery at age 5, and lost all visual perception over the next 10 years.[25] These observations suggest that absence of normal crystallin (βB2), as would be the case in a homozygote, affects normal lens development, and may directly or indirectly affect the development of other parts of the eye. The mutation results in a truncated βB2- protein that is presumably unable to associate with the normal protein to form higher order complexes.

Autosomal dominant zonular cataract[26] was mapped to chromosome 17q11-1227in a three-generation Indian family. All affected members of the pedigree presented with coexisting bilateral zonular as well as sutural opacities although there was variability in the degree of opacification. The gene mutation underlying this disease is a single-base change at one of the conserved splice junctions of the βA3/Al crystallin gene.[28] The GT dinucleotide at the donor splice site, which is 100% conserved in eukaryotes,[29] is changed to AT. This results in aberrant splicing of the mRNA such that the resulting protein is abnormal and presumably lacks the first globular domain (Kannabiran et al., unpublished data).

A missense mutation in the αA-crystallin gene is associated with zonular central cataract.[30] This mutation, which results in an amino acid substitution in a conserved region of the protein, is predicted to alter its overall charge and thereby, tertiary structure. The effect of these changes might be impaired function as chaperone or precipitation of protein due to formation of large aggregates.

Finally, a recent study identified the γD-crystallin gene to be responsible for a form of 'punctate' cataract described as juvenile-onset rather than congenital.[31]

b.'Non-crystallin cataracts

Despite the fact that a large proportion of the known cataracts are caused by mutations in various crystallin genes, there are other pathways to cataractogenesis as illustrated by the examples described below.

The connexins are gap junction proteins that are required for cell-cell communication in a number of tissues. The two major lens connexins are connexin 46 and connexin 50. Genes encoding both of these proteins have been implicated in cataracts. The connexin 46 gene when disrupted in mouse knockouts, leads to cataracts.[32] More recently, it has been found that two families with zonular pulverulent cataract, mapping to chromosome 13, have mutations in the connexin 46 gene.[50] The connexin 50 gene is mutated in a human cataract (zonular pulverulent)[33] that was originally mapped to the Duffy blood-group locus (chromosome 1) by Renwick and Lawler.[34] The initial description of this family, covering four generations, was given by Nettleship.[35] The cataract was originally described as 'lamellar' and subsequently as zonular pulverulent or as total nuclear.[36] Since the lens is avascular and metabolically inactive on differentiation of the fibres, cell-cell communication is probably required for the transport of metabolites. A recent study has concluded that the connexin channels within the lens connect the mature fibres with the differentiating fibres thus suggesting that these channels are required for lens homeostasis.[37]

[Table:3] shows that a mutation in the connexin 50 gene is also the cause of cataract in the No 2 mouse. Apart from these, the membrane proteins of the lens, MP-26 and MP-19 have been implicated in cataracts in different mutant strains of mice (see [Table:3]).

Another class of mutations that result in cataracts are those that interfere with lens development, thus resulting in loss of cellular organization. However, as suggested above, crystallins, apart from fulfilling a structural role, also affect differentiation of the lens,[38] thus indicating that a particular mutation can have more than one type of consequence. Depending on the nature of the genetic defect involved, mutations in genes that define development can result in multiple abnormalities of the eye and nervous system. An important class of developmental genes consists of the homeobox genes. These encode proteins, which have a highly conserved 60 amino acid motif known as the 'homeodomain'. These proteins regulate transcription of a number of tissue-specific genes during differentiation, and play a crucial role in body plan specification. Two homeobox genes that are associated with congenital cataract in humans in conjunction with other developmental defects are the Pax6 and PITX3 genes.

The Pax6 gene encodes a protein that is required for development of the eye. It is expressed in the neural tube, areas of the developing forebrain and hindbrain, eye, olfactory epithelium, pituitary and cerebellum. The Pax6 protein is also required for expression of several crystallin genes.[39] Mutations in Pax6 result in aniridia, a syndrome that includes cataract and is characterized by iris hypoplasia, absence of fovea, and associated abnormalities such as lens dislocation and optic nerve hypoplasia. Aniridia is inherited as an. autosomal dominant disorder.[40]

The PITX3 gene is a homeobox gene that was recently identified on the basis of its similarity to the mouse homologue, pitx3. It belongs to a family of homeobox genes, the PITX/RIEG family[41] Members of PITX/RIEG are known to play a role in eye development although the function of PITX3 itself is yet to be elucidated. Mutations in PITX3 result in autosomal dominant congenital cataracts and anterior segment mesenchymal dysgenesis (ASMD). Congenital cataracts that are associated with PITX3 mutations are described as total with no other anterior segment anomalies.[41] ASMD is a very uncommon disorder that includes all malformations of the first, second and third mesenchymal waves of the neural crest (i.e., corneal endothelium and stroma, trabecular meshwork and iris stroma.)[42]

c. Cataracts arising from chromosomal aberrations

Cataracts resulting from chromosomal translocations have been described. They are generally associated with other abnormalities since more than one gene may be disrupted by the translocation. The breakpoint of the translocation should generally contain the candidate gene. Autosomal dominant congenital cataract has been described in a three-generation family with a reciprocal translocation betweeen chromosomes 2p22 and 16pl3.[43] Congenital anterior polar cataracts have been found to result from unbalanced translocation between chromosomes 3 and 18,+44 yet another family has been reported with dominantly inherited anterior polar cataract that was associated with a balanced translocation between chromosomes 2 and 14.[45] Identification of the genes located at the breakpoints in these cases should lead to knowledge of more pathways to cataractogenesis.

In addition, a number of metabolic and developmental disorders are associated with cataract and these are reviewed elsewhere.[3]


Molecular genetic approaches to studying cataract are yielding clues into the structural and metabolic requirements for maintenance of lens transparency. Essentially, cataracts can result from changes in lens architecture, from disruption of intracellular ordered arrangement of proteins or from changes in organization of lens fibres due to aberrations in growth or differentiation. Alternatively, changes in the intracellular environment due to changes in water or small molecules can result in opacification of the lens due to breakdown of lens homeostasis. The latter type of alteration can result from abnormalities in cell-cell communication or from damage to the cell membrane. Although the pathways leading to genetic cataracts that show simple Mendelian inheritance are relatively easier to dissect, senile cataract, which represents the overwhelming majority of cataract worldwide, is a complex disease. A number of environmental influences such as UV light, oxidative and osmotic insults to the lens act in a cumulative fashion to precipitate cataractous changes.[4] Apart from these various risk factors acting as triggers, it has been hypothesized that ageing itself leads to changes in lens proteins that parallel the ageing process in other tissues. There is possibly, a genetic susceptibility to age-related cataract that would act in concert with environmental influences to cause disease.


Allele: one of the alternative forms of the same gene. An individual has two alleles for a gene, each of which is derived from one parent. In a population, there can be several alleles for a particular gene.

Apoptosis: programmed cell death, or a cell suicide response.

β-sheet: or β-pleated sheet, type of secondary structure formed by strands of polypeptide chains that can be either parallel (N and C-termini in same orientation) or antiparallel (N and C termini in opposite orientation). The β-sheet is stabilized by hydrogen bonding between amino acid side-chains of neighbouring strands.

Chromosomal translocation: type of chromosomal rearrangement in which a segment of one chromosome breaks and rejoins with a different chromosome.

Cloning: the process of creating chimeric DNA molecules (recombinant) that contain the gene of interest and a vector (vehicle), capable of propagating in an organism such as E. coli so as to obtain multiple identical copies.

Codon: a set of three bases in the genetic code that specifies an amino acid.

Genome: the entire genetic material of a cell. The human genome consists of 23 pairs of chromosomes, or 3.3 billion base pairs of DNA.

Genotype: the genetic makeup of an individual at a particular locus, i.e., it will consist of two alleles.

Heat shock protein: proteins that mediate the cellular response to environmental stress.

Heat shock proteins: bind to proteins that are unfolded due to heat or other stress, and bring about their refolding. In addition, damaged proteins are targeted for degradation by heat shock proteins. Under normal conditions, many heat shock proteins function as chaperones by assisting newly synthesized proteins in folding into their native conformations.

Heterozygous: the presence of two different alleles at a locus.

Homeobox: homeobox genes control development and differentiation by expressing a variety of 'homeodomain' proteins that in turn bind to DNA and regulate gene expression. The homeobox refers to the segment of DNA that codes for the homeodomain, which is the domain of the protein that binds DNA.

Homozygous: the presence of two identical alleles at a given locus.

Locus: the physical position of a gene in the genome.

Mendelian: trait or disorder that is inherited according to patterns consistent with its being specified by a single gene.

Microsatellite: DNA repeat sequence made up of repeat units of 2-12 base pairs in size. Microsatellites are polymorphic and show variation in the number of repeat units.

Missense: a mutation in DNA that involves a single base change and results in the substitution of one amino acid for another.

Phenotype: the total observable manifestation of a trait that is determined partly or wholly by the genotype.

Promoter: the region of a gene that regulates its transcription (RNA synthesis).

Pseudogene: a gene that is stable but inactive, derived from mutation of an ancestral active gene.

RFLP: restriction fragment length polymorphism. A polymorphism is a variation in DNA sequence that is non-pathogenic. RFLPs result from sequence alterations that either create or abolish a restriction enzyme site.

Subunit: individual polypeptide chain of proteins that contain two or more polypeptides.

Tertiary structure: the three dimensional structure of a protein that is formed by the folding of the polypeptide chain.[58]


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