disorders due to change in genes or chromosomes.
2 types: Mendelian
disorders & Chromosomal disorders.
1. Mendelian Disorders
· It is caused by alteration or mutation in the single gene.
· E.g. Haemophilia, Colour blindness, Sickle-cell anaemia, Phenylketonuria, Thalassemia, Cystic fibrosis etc.
· The pattern of inheritance of Mendelian disorders can be traced in a family by the pedigree analysis.
· Mendelian disorders may be dominant or recessive.
· Pedigree analysis helps to understand whether the trait is dominant or recessive.
Pedigree analysis of
(A) Autosomal dominant trait (E.g. Myotonic dystrophy)
(B) Autosomal recessive trait (E.g. Sickle-cell anaemia)
Haemophilia (Royal disease):
· It is a sex linked (X-linked) recessive disease.
· In this, a protein involved in the blood clotting is affected.
· A simple cut results in non-stop bleeding.
disease is controlled by 2 alleles, H & h. H is normal
allele and h is responsible for haemophilia.
Heterozygous female (carrier). She may transmit the disease to sons.
· In females, haemophilia is very rare because it happens only when mother is at least carrier and father haemophilic (unviable in the later stage of life).
· Queen Victoria was a carrier of hemophilia. So her family pedigree shows many haemophilic descendants.
· It is a sex-linked (X-linked) recessive disorder due to defect in either red or green cone of eye. It results in failure to discriminate between red and green colour.
· It is due to mutation in some genes in X chromosome.
· It occurs in 8% of males and only about 0.4% of females. This is because the genes are X-linked.
· Normal allele is dominant (C). Recessive allele (c) causes colour blindness.
· The son of a heterozygous woman (carrier, XCXc) has a 50% chance of being colour blind.
· A daughter will be colour blind only when her mother is at least a carrier and her father is colour blind (XcY).
· This is an autosome linked recessive disease.
· It can be transmitted from parents to the offspring when both the partners are carrier (heterozygous) for the gene.
· The disease is controlled by a pair of allele, HbA and HbS.
Homozygous dominant (HbAHbA): normal
Heterozygous (HbAHbS): carrier; sickle cell trait
Homozygous recessive (HbSHbS): affected
· The defect is caused by the substitution of Glutamic acid (Glu) by Valine (Val) at the sixth position of the β-globin chain of the haemoglobin (Hb).
· This is due to the single base substitution at the sixth codon of the β-globin gene from GAG to GUG.
· The mutant Hb molecule undergoes polymerization under low oxygen tension causing the change in shape of the RBC from biconcave disc to elongated sickle like structure.
· An inborn error of metabolism.
· Autosomal recessive disease.
· It is due to mutation of a gene that codes for the enzyme phenyl alanine hydroxylase. This enzyme converts an amino acid phenylalanine into tyrosine.
· The affected individual lacks this enzyme. As a result, phenylalanine accumulates and converts into phenyl pyruvic acid and other derivatives.
· They accumulate in brain resulting in mental retardation. These are also excreted through urine because of poor absorption by kidney.
· An autosome-linked recessive blood disease.
· It is transmitted from unaffected carrier (heterozygous) parents to offspring.
· It is due to mutation or deletion.
· It results in reduced synthesis of a or b globin chains of haemoglobin. It forms abnormal haemoglobin and causes anaemia.
· Based on the chain affected, thalassemia is 2 types:
o a Thalassemia: Here, production of a globin chain is affected. It is controlled by two closely linked genes HBA1 & HBA2 on chromosome 16 of each parent. Mutation or deletion of one or more of the four genes causes the disease. The more genes affected, the less a globin molecules produced.
o b Thalassemia: Here, production of b globin chain is affected. It is controlled by a single gene HBB on chromosome 11 of each parent. Mutation of one or both the genes causes the disease.
· Thalassemia is a quantitative problem (synthesise very less globin molecules). Sickle-cell anaemia is a qualitative problem (synthesise incorrectly functioning globin).
2. Chromosomal disorders
They are caused due to absence or excess or abnormal arrangement of one or more chromosomes. 2 types:
a. Aneuploidy: The gain or loss of chromosomes due to failure of segregation of chromatids during cell division.
b. Polyploidy (Euploidy): It is an increase in a whole set of chromosomes due to failure of cytokinesis after telophase stage of cell division. This is very rare in human but often seen in plants.
Examples for chromosomal disorders
§ Down’s syndrome: It is the presence of an additional copy of chromosome number 21 (trisomy of 21).
Genetic constitution: 45 A + XX or 45 A + XY (i.e. 47 chromosomes).
o They are short statured with small round head.
o Broad flat face.
o Furrowed big tongue and partially open mouth.
o Many “loops” on finger tips.
o Broad palm with characteristic palm simian crease.
o Retarded physical, psychomotor & mental development.
o Congenital heart disease.
§ Klinefelter’s Syndrome: It is the presence of an additional copy of X-chromosome in male (trisomy).
Genetic constitution: 44 A + XXY (i.e. 47 chromosomes).
o Overall masculine development. However, the feminine development is also expressed. E.g. Development of breast (Gynaecomastia).
o Mentally retarded.
§ Turner’s syndrome: This is the absence of one X chromosome in female (monosomy).
Genetic constitution: 44 A + X0 (i.e. 45 chromosomes).
o Sterile, Ovaries are rudimentary.
o Lack of other secondary sexual characters.
o Mentally retarded.