Introduction to Genetics

Introduction to Genetics

• Genetics is the study of genes and heredity, which are the mechanisms by which traits are passed from parents to offspring.
• The genome is the entire genetic material of an organism, including DNA, RNA, and associated proteins.
• DNA is the molecule that carries genetic information and is composed of two linked strands in a double helix shape.
• Each strand has a backbone of alternating sugar (deoxyribose) and phosphate groups.
• Attached to each sugar is one of four nitrogen bases: adenine (A), cytosine (C), guanine (G), or thymine (T).
• The human genome contains approximately 3.2 billion nucleotides.
• A trinucleotide base is called a codon.
• There are 64 codons, with 61 encoding for amino acid synthesis and 3 acting as stop codons.
• Humans have 20 amino acids.
• A gene is a specific sequence of nucleotides within the genome.
• There are about 20,000 protein-encoding genes in the human genome, making up 1.5% of the genome.
• Exons are coding sequences of the gene.
• Introns are non-coding sequences in the gene.
• A locus is the location of a gene on a chromosome.
• Genotype refers to the genetic makeup passed between generations.
• Phenotype refers to the observable characteristics or traits of an organism.
• Hereditary disorders are passed from parents to offspring through gametes, making them familial.
• Congenital means present at birth, but not all genetic disorders are congenital.

Classification of Genetic Disorders

• Genetic disorders are categorized as classical or non-classical.
• Classical genetic diseases include chromosomal disorders, single gene disorders (Mendelian Disorders), and multifactorial disorders.
• Non-classical genetic diseases or single gene disorders with atypical inheritance patterns include mitochondrial gene mutations, triplet repeat mutations, uniparental disomy, genomic imprinting, and gonadal mosaicism.

Chromosomal Disorders

• Approximately 1 in 200 newborn infants is affected by a chromosomal abnormality, with a higher incidence in fetuses that do not survive to term.
• Cytogenetic disorders involve alterations in the number or structure of chromosomes and can affect autosomes or sex chromosomes.
• These abnormalities can be either numerical or structural.

Numerical Abnormalities in Chromosomes

• Euploidy is a normal chromosome count that is an exact multiple of the haploid number (n).
• Aneuploidy is a gain or loss of one or more individual chromosomes.
• Polyploidy involves a gain of entire sets of chromosomes, such as triploidy (3n) and tetraploidy (4n).
• Trisomy refers to an extra copy of a specific autosome, such as in Down syndrome (trisomy 21).
• Monosomy refers to having only one copy of a specific chromosome, like in Turner Syndrome (45,X).
• Non-disjunction, the failure of homologous chromosomes to separate during cell division (meiosis), results in gametes with an extra chromosome (n+1) or one less chromosome (n-1).
• Anaphase lag occurs when a chromosome or chromatid lags behind during division, leading to one normal cell and one with monosomy.

Mosaicism

• Mosaicism refers to the presence of two or more distinct cell populations with different chromosome numbers within an individual's body.
• It can arise from post-zygotic mitotic chromosome errors or pre-existing paternal aneuploidy of meiotic origin.

Structural Abnormalities in Chromosomes

• Structural abnormalities result from chromosomal breakage followed by loss or rearrangement of material.
• These abnormalities include deletions, duplications, inversions, translocations, and isochromosomes.

Deletions

• Deletion involves the loss of a chromosome segment.
• Terminal deletions occur when one break results in the loss of the distal portion.
• Interstitial deletions involve the loss of a segment between two breaks.

Duplications

• Duplication involves the presence of an extra copy of a chromosome segment.
• It can result in an overabundance of certain genes, leading to genetic disorders or variations.

Inversions

• An inversion occurs when a chromosome segment is flipped or reversed in orientation.
• Pericentric inversions involve the centromere, while paracentric inversions do not.

Translocations

• Translocation occurs when two non-homologous chromosomes exchange segments of genetic material.
• Reciprocal translocations involve the exchange of segments between two non-homologous chromosomes.
• Robertsonian translocations involve the fusion of two acrocentric chromosomes, resulting in a single larger chromosome and a smaller fragment.

Isochromosomes

• Isochromosomes are abnormal chromosomes with two identical arms, typically formed due to an error in chromosome division.

Clinical Examples of Chromosomal Abnormalities

Disorders of Autosomal Chromosomes

• Trisomy (21, 18, 13) are responsible for Down syndrome, Edwards syndrome, and Patau syndrome, respectively.
• Deletion, as seen in Cri du chat syndrome, involves chromosome 5.

Trisomy 21 (Down's Syndrome)

• The most common chromosomal disorder, with different cytogenetic types.
• 95% of cases are due to regular trisomy 21, caused by non-disjunction.
• The extra chromosome typically originates from the mother.
• Incidence significantly increases with maternal age.
• Translocation Down's Syndrome represents 4% of cases, with extra chromosomal material attached to chromosome 22 or 14, 15, often familial.
• Isochromosome '21' is rare but can result in Down's syndrome, involving duplication of the long arm of chromosome 21.
• Mosaic Down's Syndrome, accounting for 1% of cases, involves a mix of 47 and 46 chromosomes, with varying symptom severity.

Abnormalities of Sex Chromosomes

• Klinefelter syndrome (47,XXY) affects males with two or more X chromosomes, typically XXY.
• It is not inherited and is caused by a cell division error during fetal development.
• Turner syndrome (45,X0) affects females with a missing or partially missing second X chromosome.
• It occurs in one out of 2,000 female births and is linked to 10% of miscarriages.