This article is on the genetic disorders in humans. Before going into the details of the topic, we must know some of the terms related to genetic disorders. Here we will learn about Mutation and its types, Chromosomal Abbreviation and Genomic Mutation and its types. Then we will discuss in details the two types of genetic disorders in humans- one is the Mendelian Disorders and the other is the Chromosomal Disorders.
The discontinuous (either spontaneous, induced or gradual) variations observed in the genotype, at the level of chromosomes, genes and DNA and thus the phenotypic expression of biotic organisms over a generation is termed as the mutation.
Types of Mutations
Based on the origin and cause, mutations in biotic organisms are of the following types:
Variations in the DNA molecules due to alterations in the sequence of nucleotides results in the mutation of the gene.
Point mutation: Single base pair alteration within the DNA molecule. E.g. Sickle cell anaemia.
Gross mutation: Alterations in more than one nucleotide pair within the DNA molecule.
The process of gene mutation is of the following types
i. Deletion: Complete erasing/removal of one/single or more than one bases from the nucleotide sequence of DNA.
E.g. For a gene sequence AAGCTA, removal of A results in A GCTA.
ii. Insertion/Addition: Adding of one/single or more than one bases in the nucleotide sequence of DNA.
E.g. For a gene sequence AAGCTA, addition of C results in AACGCTA.
Chromosomes are composed of proteins, RNA and DNA. DNA exists in the highly supercoiled, double helical form in the chromosomes. Hence, alterations in chromosomes can occur due to deletions, insertions or duplications in DNA sequences which finally results in the manifestation of chromosomal aberrations or abnormalities at both genotypic and phenotypic level. An important hallmark of cancer cells is the occurrence of chromosomal aberrations.
Alterations in the number of chromosomes resulting in the manifestation of actual, visible phenotypic symptoms/effects.
Genomic mutations are of following broad types-
Significant alteration in the chromosomal number of an organism due to non-disjunction/non-separation of the two chromosomes [2n – One (n) each] in the homologous pair during cell division so that one of the resulting gametes possess an extra chromosome (n+1) with the other gamete lacking a chromosome (n-1).
Alterations in the chromosomal number resulting in multiple copies of the basic set or pair of chromosomes affecting the genomic constitution of the organism ultimately resulting in genetic variations.
i. Haploidy: Only a single set of chromosome (n) present. Haploid organisms are preferred for studying the effects of mutation since the manifestation of all the mutations which are either dominant or recessive along (possible lethal effects of single copies) is very rapid due to the presence of only a single allele or gene.
ii. Polyploidy: More than diploid (2n) set of chromosomes.
This condition results due to the deficiency in cytokinesis during cell division resulting in an elevation in the chromosomal set of the organism.
E.g. Mostly seen in plants. In fact, commercially employed wheat used for making bread is hexaploid (6n) while members of genus Brassica are tetraploid (4n). When present in animals it mostly leads to sterility and therefore is not very common.
Genetic Disorders In Humans
The genetic disorders are classified into two types- Mendelian disorder and Chromosomal disorder.
Mendelian Disorder or Sex-Linked Inheritance – First Type of Genetic Disorders
It is a sex-linked recessive disease that shows its transmission from unaffected carrier female to some of the male progeny. In haemophilia, a single protein that is a part of the cascade of proteins involved in the clotting of blood is affected. Because of this, a simple cut will result in non-stop bleeding in an affected individual. The heterozygous female (carrier) for haemophilia may transmit the disease to sons.
The possibility of a female becoming haemophilic is extremely rare because the mother of such a female has to be at least carrier and the father should be haemophilic (unviable in the later stage of life). The family pedigree of Queen Victoria shows a number of haemophilic descendants as she was a carrier of the disease.
2. Colour Blindness
Colour blindness is a common inherited sex-linked disorder. It is a condition that affects a person’s ability to see or distinguish certain colours. The genes that produce red and green light-sensitive proteins are located on the X chromosome. Mutations in these genes can cause colour blindness. The gene for colour blindness is recessive to the gene for normal sight. As the males possess only one X chromosome and, therefore, only a single sex-linked gene at each locus, they are said to be hemizygous. The females, however, with two sex-linked genes, can be either homozygous or heterozygous.
Cross A: If a colour blind man (XCY) marries a girl with normal vision (XX), the daughters would have normal vision but would be the carrier, while sons would also be normal.
Cross B: If the carrier girl (heterozygous for colour blindness, XCX) now marries a colour blind man XCY, the offspring would show 50% females and 50% males. Of the females, 50% would be the carrier for colour blindness and the rest 50% would be colour blind. Of the males, 50% would have normal vision and the 50% would be colour blind.
3. Sickle-Cell Anaemia
An autosomal recessive disorder that is genetically transmitted to progenies from affected parents when both the father and mother of the progenies are the heterozygous carrier for the gene. The single pair of alleles of gene HbA (normal form) and HbS (sickle form) govern sickle-cell anaemia, which results in the occurrence of three possible genotypes
i. Combination of HbA X HbA (Normal, non-carrier, homozygous) − 100% disease free
ii. Combination of HbA X HbS (Normal, carrier, heterozygous) − 50% probability of transmitting faulty HbS gene
iii. Combination of HbS X HbS (Homozygous, progeny weak and die before reaching maturity)
Mutation (transversion) of the HbA gene which encodes for the β-chain of haemoglobin resulting in a single change in the amino acid arrangement of the β-chain forms the HbS allele. At the 6th position of the β-chain, the non-polar amino acid valine replaces the negatively charged, polar amino acid glutamic acid. HbS encodes for the haemoglobin molecules which are capable of undergoing polymerization under lower oxygen tension
altering the shape of RBC from a biconcave disc into a sickle-shaped structure.
Chromosomal Disorders in Humans – Another Type of Genetic Disorders
The chromosomal disorders are caused due to excess or absence or abnormal arrangement of one or more chromosomes.
1. Down’s Syndrome
The nucleus of each cell typically contains 23 pairs of chromosomes, half of which are inherited from each parent. When an individual has a full or partial extra copy of chromosome 21, then Down syndrome occurs. This failure of segregation of chromatids during cell division cycle results in the gain or loss of a chromosome(s), called aneuploidy.
It was first described in 1866 by Langdon Down. The disorder develops due to trisomy of chromosome number 21. The trisomic condition arises due to the formation of n+1 male or female gamete by non-disjunction and the subsequent fertilization by a normal (n) gamete. It is characterized by:
a. Short stature
b. Small round head
c. Furrowed tongue
d. Partially open mouth
e. Broad palm with characteristic palm crease
f. Many ‘loops’ on fingertips
g. Big and wrinkled tongue
h. Physical (underdeveloped gonads and genitals, loose joints), psychomotor and mental development
2. Turner’s Syndrome
It is a chromosomal condition that affects development in females. The disorder is due to monosomy. It appears due to the fusion of abnormal egg (22+0) and a normal sperm (22+X) or a normal egg (22+X) and abnormal sperm (22+0). Such females are sterile as ovaries are rudimentary besides other features including lack of other secondary sexual characters.
3. Klinefelter’s Syndrome
It is caused due to the presence of an additional copy of X-chromosome resulting in 44+XXY type chromosome complement. The defect appears due to the union of an abnormal egg (22+XX) and a normal sperm (22+Y) or normal egg (22+X) and abnormal sperm (22+XY). Such persons are sterile males with overall masculine development and some female characteristics E.g. Feminine pitched voice, development of breast or gynaecomastia.
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