RPSC CLASS: with pleiotropy, penetrance and expressivity

Comprehensive Genetics Concepts: Linkage, Crossing Over, and Mutations

1. Linkage

Definition

Linkage is the tendency of genes to remain together in their original combination during inheritance. Linked genes are transmitted together and do not assort independently, thus violating Mendel’s law of independent assortment.

Key Concepts

• Linkage Group: All genes located on a given pair of chromosomes constitute a linkage group.
• The number of linkage groups equals the haploid number of chromosomes for a species.
• Maximum Number of linkage groups = haploid no. of chromosomes of a species
• Example: Humans have 23 linkage groups (46/2 = 23).
• Complete Linkage: When genes are very closely placed on a chromosome and are always transmitted together without recombination.
• Incomplete Linkage: When linked genes can separate due to crossing over, leading to new combinations of linked genes.

Important Details

• Linkage reduces genetic variability.
• The strength of linkage depends on the distance between genes; closer genes have stronger linkage.
• Linkage can be determined from test cross progeny data.
• Linkage was first reported by Bateson and Punnet in 1906.
• T.H. Morgan developed the theory of linkage – concluded that coupling and uncoupling were the two phases of linkage.

Classification of Linkage

Based on Crossing Over

• Complete Linkage:
  • Occurs when genes are very closely placed on a chromosome.
  • These genes are always transmitted together and do not assort independently.
  • Example: Observed in male Drosophila, where there is a complete absence of recombinant types due to the lack of crossing over.
• Incomplete Linkage:
  • Occurs when genes are located farther apart on a chromosome.
  • Allows formation of new or non-parental combinations of linked genes due to crossing over.
  • Example: Observed in maize, pea, and female Drosophila.

Based on Genes Involved

• Coupling Phase:
  • When two dominant alleles are on the same chromosome, and the two recessive alleles are on the other member of the chromosome pair.
  • Designated as AB/ab.
• Repulsion Phase:
  • When one dominant and one recessive allele are on the same chromosome, and the other dominant and recessive alleles are on the other member of the chromosome pair.
  • Designated as Ab/aB.

Based on Chromosomes

• Autosomal Linkage:
  • Refers to the linkage of genes located on autosomes (chromosomes other than sex chromosomes).
• Allosomal Linkage (Sex Linkage):
  • Refers to the linkage of genes located on sex chromosomes, primarily the X chromosome.
  • This type of linkage is gender-specific and often involves traits linked to the X chromosome.

Examples

• Drosophila:
• Males show complete linkage due to the absence of crossing over – no recombinant types seen
• Females show incomplete linkage – leads to crossing over and generation of recombinant type progeny
• Maize (Corn), Pea plants: Incomplete linkage

Applications

• Linkage analysis is used in breeding programs to select for desirable traits.
• In medical genetics, linkage can help identify genes associated with diseases.

2. Crossing Over

Definition

Crossing Over is the reciprocal exchange of segments between non-sister chromatids of homologous chromosomes during meiosis, leading to genetic recombination.

Key Concepts

• Recombination: The process of forming new combinations of genes due to crossing over.
• Frequency of recombination ∝ distance between two genes
• Longer the distance between two genes, higher the chance of recombination
• The maximum frequency of recombination does not exceed 50%
• Chiasmata: The physical points where crossing over occurs.
• Synapsis: The pairing of homologous chromosomes during Prophase I of meiosis.
• Interference: One crossover reduces the chance of another nearby crossover. Positive and negative interference affect genetic mapping.
• Parental/Non-crossover/non-recombinant types: Gametes/individuals carrying original or parental combination of genes
• Non-parental/Crossover/Recombinant types: Gametes or individuals carrying new combination of genes arising from crossing over

Types of Crossing Over

Depending upon the number of chiasmata involved, crossing over may be of three types:

1. Single Crossing Over: Single chiasma formation between non-sister chromatids – involves only two chromatids out of four
2. Double Crossing Over: Formation of two chiasmata between non-sister chromatids – involves either two/three/four strands
3. Multiple Crossing Over: More than two cross-overs between non-sister chromatids – frequency of occurrence is extremely low

Important Details

• Synaptonemal complex: A protein structure that forms between homologous chromosomes (two pairs of sister chromatids) during meiosis and is thought to mediate synapsis and recombination during meiosis in eukaryotes. It holds the homologues together during crossing-over.
• Crossing over occurs during the Pachytene stage of Prophase I in meiosis.
• It increases genetic diversity by creating new combinations of alleles.

Examples

• In maize, crossing over can be observed during meiosis, leading to genetic variation in offspring.

Applications

• Crossing over is essential for genetic mapping and is used in breeding programs to introduce genetic variation.
• It helps in locating genes on chromosomes, thus aiding in the construction of linkage maps.

3. Mutations

Definition

Mutation is a change in the gene, potentially capable of being transmitted. It can be defined as sudden, stable, discontinuous, and inheritable variations that appear in an organism due to a permanent change in their genotype.

Historical Background

• The first scientific study of mutation was reported in 1910 by T.H. Morgan, who obtained white-eyed Drosophila in a culture of red-eyed flies.
• Mutation was first observed in animals in 1791 by Seth Wright, who noted hornless cattle appearing in breeds of horned cattle.
• The idea of mutation originated from the observations of Dutch botanist Hugo de Vries (1880) on variations in plants of Oenothera lamarckiana.

Types of Mutations

1. Gene Mutations
2. Chromosomal Mutations
3. Genomic Mutations

Classification of Gene Mutations

Based on Origin

• Germline Mutations:
  • Present in the parent’s egg or sperm cells (germ cells).
  • When an egg and a sperm cell unite, the resulting fertilized egg cell receives DNA from both parents. If this DNA has a mutation, the child will have the mutation in each of his or her cells.
• Acquired (Somatic) Mutations:
  • Occur at some time during a person’s life and are present only in certain cells, not in every cell of the body.
  • Can be caused by environmental factors such as ultraviolet radiation from the sun or can occur if an error is made as DNA copies itself during cell division.

Based on Cause

• Spontaneous Mutations: Occur naturally without a known cause.
• Induced Mutations: Occur due to exposure to physical or chemical agents that increase the frequency of mutations.

Specific Types of Gene Mutations

• Point Mutation: A change in a single nucleotide in the DNA sequence.
  • Substitutions (Replacements):
  • Transition: A purine (adenine or guanine) is replaced by another purine, or a pyrimidine (cytosine or thymine) is replaced by another pyrimidine.
    • Example: GC→AT or AT→GC
  • Transversion: A purine is replaced by a pyrimidine or vice versa.
    • Example: GC→CG or TA, AT→TA or CG
• Frame Shift Mutation:
  • Caused by the addition or deletion of a single nucleotide, which shifts the reading frame of the genetic code.
  • This results in a completely different translation from the original, often leading to nonfunctional proteins.

Chromosomal Mutations or Aberrations

These mutations alter the number or position of existing genes on chromosomes and may involve modifications in chromosome morphology or number.

Deletion or Deficiency:

• A segment of a chromosome breaks off and is lost.
• Example: Deletion of a segment of chromosome number 5 causes Cri-du-chat syndrome in humans.

Duplication:

• A chromosomal segment is duplicated, resulting in repeated genes on the same chromosome.

Inversion:

• A segment of a chromosome is removed and rejoined in reverse order.
• Example: A chromosome with gene order A, B, C, D, E, F, G, H may have an inversion resulting in A, D, C, B, E, F, G, H.

Translocation:

• A segment of one chromosome breaks and is transferred to another non-homologous chromosome.
• Robertsonian Translocations: These involve the fusion of two acrocentric chromosomes at their centromeres to form a single metacentric chromosome. Such rearrangements are common in mammals and can lead to variations in chromosome numbers across species.

Numerical Aberrations of Chromosomes

Euploidy:

• The somatic chromosome number is an exact multiple of the basic haploid number.
• Types:
  • Haploidy: Organism has one set of chromosomes.
  • Polyploidy: Organism has more than two sets of chromosomes.
  • Autopolyploidy: Increase of the same genome (e.g., Autotriploid in maize).
  • Allopolyploidy: Developed through hybridization between two species followed by chromosome doubling (e.g., Wheat).

Aneuploidy:

• Involves the loss (hypoploidy) or addition (hyperploidy) of one or more chromosomes.
• Types:
  • Monosomy: Missing one chromosome (e.g., Turner’s syndrome, 44+X).
  • Nullisomy: Loss of a chromosome pair, usually lethal in diploids (2n – 2).
  • Trisomy: Extra chromosome (e.g., Down’s syndrome, 45+XX or 45+XY; Klinefelter’s syndrome, 44+XXY).
  • Tetrasomy: Particular chromosome is represented four times in a diploid complement (2n + 2).

Disorders Associated with Chromosomal Mutations

• Turner’s Syndrome: Monosomy for sex chromosomes (XO), 2n – 1 = 45.
• Klinefelter’s Syndrome: Trisomy of sex chromosomes (XXY), 2n + 1 = 47.
• Criminal’s or Jacob’s Syndrome (Super Males): Extra Y chromosome in males (XYY), 2n + 1 = 47.
• Down’s Syndrome: Trisomy of chromosome 21.
• Edward’s Syndrome: Trisomy of chromosome 18.
• Patau’s Syndrome: Trisomy of chromosome 13.