Karyotype and Mutation

Karyotype and Mutation

• Cytogenetics studies chromosomes and diseases related to changes in their number and structure
• It analyzes chromosomes structure and function to diagnose genetic conditions and identify abnormalities from chromosomal changes

Karyotyping

• Karyotyping examines chromosomes in a cell sample to identify genetic disorders
• It involves producing a karyotype, arranging chromosome pairs by size and length, and identifying abnormalities in chromosome number or structure
• Karyotyping is based on the size of chromatids, banding pattern, and centromeric position

Genetic Disorders Identified Through Karyotyping:

• Genetic disorders identified through karyotyping include Down Syndrome (Trisomy 21)
• Patau Syndrome (Trisomy 13)
• Edwards Syndrome (Trisomy 18)
• Klinefelter Syndrome (47, XXY)
• Turner Syndrome (45, X)

Types of Centromere Positions:

• Metacentric: Centromere is in the middle
• Submetacentric: Centromere is slightly higher than the middle
• Acrocentric: Centromere is near the top with a very short p-arm and long q-arm
• Telocentric: Centromere is at the very top, with no p-arm and a long q-arm (only in animals, not humans)

Cell Lines in Laboratory Research

• Cell lines divide and grow continuously for multiple generations
• They are used for species identification, indexing genome stability, validating normal diploid karyotypes (46 chromosomes), and detecting numerical and structural chromosome abnormalities

Detecting Numerical Chromosome Abnormalities:

• Aneuploidy: Abnormal chromosome number
• Monosomy: A missing chromosome from a pair
• Trisomy: An extra chromosome in a pair

Detecting Structural Abnormalities:

• Deletion: A missing segment of DNA
• Duplication: An extra copy of a DNA segment
• Translocation: Exchange of chromosome segments
• Inversion: A reversed segment of a chromosome

Karyotyping Process:

• Sample Collection: A blood sample is collected, and white blood cells are used
• Cell Culture: Cells are cultured in a laboratory
• Centrifugation: Separates white blood cells from other blood components
• Chromosome Preparation: A chemical (colchicine) is added to stop cells at metaphase and staining is performed to visualize chromosomes
• Karyotype Analysis: Chromosomes are photographed, printed, cut, and arranged into homologous pairs

Types of Karyotyping Techniques:

• Fluorescent In Situ Hybridization (FISH): Detects specific chromosome markers for abnormalities
• Ideogram Mapping: Uses staining techniques to create diagrammatic representations of chromosome banding patterns

Normal vs. Abnormal Karyotypes:

• A normal karyotype has 46 chromosomes (22 pairs of autosomes + 2 sex chromosomes)
• Abnormalities, like Down Syndrome (Trisomy 21), occur due to nondisjunction

Down Syndrome (Trisomy 21) Characteristics:

• Characteristics include muscle weakness, upward slanting eyes, intellectual disabilities (IQ often below 50), small head, ears, and mouth, a round face with a short neck and arms, a flattened nasal bridge, and small, irregular teeth

Prenatal Genetic Testing

• Prenatal testing can detect genetic disorders before birth, through methods like Amniocentesis, Blood Sampling, and Chorionic Villus Sampling (CVS)

Types of Mutation:

• Point Mutation: A single nucleotide base is changed
• Deletion: A segment of DNA is missing, which can be fatal
• Translocation: A segment of one chromosome moves to another
• Inversion: A segment of DNA is flipped in orientation
• Insertion: Additional DNA segments are inserted into a sequence
• Duplication: A fragment of one chromosome attaches to a homologous chromosome

DNA Discovery and Structure:

• DNA was identified by Friedrich Miescher and its structure was discovered in 1953 by James Watson and Francis Crick
• Each nucleotide has a phosphate group, a 5-carbon sugar (deoxyribose), and a nitrogen-containing base
• Nucleotides link via phosphodiester bonds to form polymer nucleic acids

DNA Bonding and Bases:

• Phosphodiester bonds link nucleotides, forming the sugar-phosphate backbone
• Hydrogen bonding occurs between nitrogenous bases paired complementarily
• Adenine (A) pairs with Thymine (T), forming two hydrogen bonds
• Cytosine (C) pairs with Guanine (G), forming three hydrogen bonds
• Purines (double-ring structures) consists of Adenine (A) and Guanine (G)
• Pyrimidines (single-ring structures) compromise Cytosine (C), Thymine (T), and Uracil (U)

Sugar-Phosphate Backbone:

• DNA strands are antiparallel
• The left strand runs from 5' (5-prime) to 3' (3-prime)
• The right strand runs from 3' (3-prime) to 5' (5-prime)
• The 5' end refers to the location of the carbon atom at the top, while the 3' end refers to the exposed lower part

Helical Structure of DNA:

• DNA has a double-helical structure
• Rosalind Franklin's X-ray diffraction photograph showed DNA's twisted shape

Sequence of DNA:

• The nitrogenous base sequence along a gene determines the amino acid sequence of a protein
• A defective gene may have an error in the DNA sequence
• A single mutation might result in a faulty protein, with beneficial, neutral, or detrimental effects

The Human Genome Project:

• The Human Genome Project identified all base pairs in the human genome
• The project took 50 years to complete and the human genome contains 3.2 billion base pairs

Learn about cytogenetics, which studies chromosomes and diseases related to changes in their structure and number. Karyotyping examines chromosomes in a cell sample to identify genetic disorders like Down Syndrome, Patau Syndrome and several others.