Genetic Disorder Chapter Notes | Biology for Grade 11 PDF Download

Chromosomal Abnormalities and Syndromes

• Chromosomal abnormalities occur due to environmental factors (e.g., radiation, food intake) or internal genetic conditions, affecting chromosome structure or number.
• Structural chromosomal abnormalities involve changes in chromosome structure, while numerical abnormalities involve changes in chromosome number.
• Monosomy is the absence of one chromosome from a pair (2n-1), e.g., monosomy of chromosome 1.
• Trisomy occurs when a chromosome is present in three copies (2n+1), e.g., trisomy of chromosome X.
• Both monosomy and trisomy are types of aneuploidy, where one or a few chromosomes are absent or present in multiple copies.
• Polyploidy involves multiplication of the entire chromosome set, e.g., 69 chromosomes (23 × 3) or 92 chromosomes (23 × 4).
• Polyploidy is common in plants; examples include hexaploid bread wheat (six sets), tetraploid cabbages and mustards (four sets), triploid bananas and apples (three sets), and octoploid strawberries and sugar cane (eight sets).
• Structural or numerical changes can lead to significant phenotypic changes, manifesting as diseases or syndromes.

Structural Chromosomal Abnormalities

• Deletion: A segment of a chromosome breaks away, shortening the chromosome. For example, retinoblastoma is caused by deletion of a portion of chromosome 13. Deletion of both ends of a chromosome can result in a ring chromosome.
• Duplication: A segment of a chromosome is repeated, lengthening the chromosome. For example, Charcot-Marie-Tooth disease is caused by duplication of genes on chromosome 17.
• Inversion: A chromosome segment breaks away, reverses its orientation by 180 degrees, and reattaches. The chromosome length remains unchanged, but gene orientation is reversed. For example, RCAD syndrome is caused by inversion of a segment of chromosome 17.
• Translocation: A chromosome segment breaks away and attaches to another chromosome. Reciprocal translocation involves mutual exchange between two chromosomes, e.g., Burkitt’s lymphoma due to exchange between chromosomes 8 and 14. Robertsonian translocation involves attachment without mutual exchange, potentially reducing chromosome number.

Numerical Chromosomal Abnormalities

• Numerical abnormalities result in syndromes or diseases due to changes in chromosome number.
• A syndrome is a group of symptoms that consistently occur together, while a disease is an abnormal physiological response to internal or external factors, e.g., fever caused by microbes.
• Down’s Syndrome:
  • Incidence: Approximately 1 in 800 live births.
  • Chromosomal basis: Caused by trisomy 21, where chromosome 21 is present in three copies instead of two. Karyotype is 47, XX, +21 (females) or 47, XY, +21 (males).
  • Trisomy 21 results from nondisjunction, an error in cell division where chromosomes fail to separate during meiosis.
  • Risk increases with maternal age; over 85% of Down’s syndrome babies are born to mothers over 35 years at pregnancy.
  • Clinical symptoms: Flat face, slanting eyes, small mouth, protruding tongue, flattened nose, short neck, short arms and legs, single deep palmar crease, low IQ, stunted growth, muscular hypotonia, underdeveloped gonads, and issues with breathing, heart, or hearing.
  • Diagnosis: Identified by an extra chromosome 21 in the karyotype.
  • Treatment: No standard treatment; tailored to individual conditions. Early interventions include speech therapy, physiotherapy, and nutritional supplements. Life expectancy has increased from 9 years in the early 1900s to 60 years or more with modern diagnostics and treatments.
• Klinefelter’s Syndrome:
  • Incidence: Approximately 1 in 1,000 newborn males.
  • Chromosomal basis: Genotype 47, XXY, affecting males. Arises from nondisjunction of the X chromosome during meiosis, where the X chromosome fails to separate, leading to an XX ovum fertilized by a Y sperm.
  • Not inherited; a Klinefelter father cannot pass the condition to his newborn.
  • Clinical symptoms: Unusually tall stature, reduced facial and body hair, smaller testes, enlarged breasts, and coarse voice.
  • Diagnosis: Often detected via Barr body test of buccal smear, where one Barr body indicates an extra X chromosome (normal males have none).
  • Symptoms are subtle at birth but become noticeable at puberty.
  • Treatment: Testosterone therapy to enhance masculine features and psychological counseling to manage depression and aggression.
• Turner’s Syndrome:
  • Incidence: 1 in 2,500 newborn girls, frequently observed in miscarriages and stillbirths.
  • Chromosomal basis: Monosomy X, with a missing X chromosome in females, resulting in karyotype 45, X. Caused by nondisjunction during meiosis, producing an ovum with no X chromosome, which fuses with a sperm carrying one X chromosome.
  • Not inherited; mothers with Turner’s syndrome cannot pass it to daughters.
  • Clinical symptoms: Short stature, webbed neck (loose neck skin), small breasts, low-set ears, swollen hands and feet, underdeveloped ovaries, and absence of menstrual periods.
  • Diagnosis: Prenatal diagnosis via amniocentesis or chorionic villus sampling. Postnatally, absence of Barr body in buccal smear prompts further investigation.
  • Treatment: No permanent cure. Hormone therapy (androgen and estrogen) supports growth and ovarian function.

Monogenic Disorders and Pedigree Mapping

• Monogenic disorders are caused by a mutation in a single gene, with over 10,000 such diseases affecting millions worldwide.
• The disease’s signs and symptoms depend on the function of the defective gene.
• Monogenic disorders follow Mendel’s laws of inheritance but can also arise from spontaneous mutations without family history.
• A single mutation in one gene can cause a specific disease (e.g., sickle cell anemia), or multiple mutations in one gene can produce the same disease (e.g., cystic fibrosis with over 200 mutation types).
• Classification of Monogenic Disorders:
  • Autosomal Recessive: Requires two copies of the defective gene (one from each parent) to express the disorder. Carriers with one defective and one normal gene are unaffected. Examples include sickle cell anemia, cystic fibrosis, Tay-Sachs disease, and phenylketonuria.
  • Autosomal Dominant: A single defective gene is sufficient to cause the disorder. Examples include achondroplasia and Huntington’s disease.
  • X-linked Recessive: Affects males primarily, as the defective gene is on the X chromosome. Carrier females (XX) are unaffected, but males (XY) express the disorder. Examples include haemophilia and Duchenne muscular dystrophy.
  • X-linked Dominant: Affects both males and females, with affected males passing the mutation to all daughters but not sons. Examples include hypophosphatemia and Alport syndrome.
• Pedigree Analysis: Interpretation of family tree data to diagnose inherited genetic diseases. Uses specific symbols to represent family relationships and disease status.
• Autosomal Recessive Disorders:
  • Two defective gene copies are needed for the disorder; carriers (one defective, one normal gene) are unaffected.
  • Humans carry about 5 or more defective recessive genes that could cause disease.
  • Sickle Cell Anemia: Caused by a mutation in the hemoglobin-β gene on chromosome 11, producing defective hemoglobin (Hb). After releasing oxygen, defective Hb forms rod-like structures, causing red blood cells to become stiff and sickle-shaped.
  • Genotypes: Affected individuals have s/s (homozygous recessive), unaffected are S/S (homozygous dominant) or S/s (heterozygous carriers).
  • Common in populations from sub-Saharan Africa, South America, Cuba, Central America, Saudi Arabia, India, and Mediterranean countries. In India, prevalent in the Deccan plateau and parts of Kerala and Tamil Nadu.
  • Cystic Fibrosis: Caused by mutations in a single gene, producing thick, sticky mucus that damages organs, especially lungs, leading to chronic infections.
  • Tay-Sachs Disease: Results from the absence of hexosaminidase A enzyme, causing fatty substance accumulation in nerve cells, particularly in the brain. Fatal in childhood, with 1 in 27 Ashkenazi Jewish individuals carrying the gene.
  • Phenylketonuria: Caused by a mutation in the phenylalanine hydroxylase gene, increasing phenylalanine levels in the blood.
• Autosomal Dominant Disorders:
  • The defective allele is dominant, and the normal allele is recessive.
  • Achondroplasia: Causes dwarfism. Normal individuals have genotype d/d, mildly affected have D/d, and severely affected have D/D (often lethal). Most surviving cases are heterozygotes (D/d).
  • Huntington’s Disease: A rare disorder affecting the nervous system.
• X-linked Recessive Disorders:
  • The defective gene is on the X chromosome, with carrier females (XX) unaffected and males (XY) expressing the disorder.
  • Affected males pass the defective X to all daughters (who become carriers) but not to sons (who inherit the Y chromosome).
  • Haemophilia: A bleeding disorder due to mutations in coagulation factor VIII (type A) or IX (type B) genes, resulting in abnormal or reduced coagulation factors, leading to spontaneous bleeding or increased bleeding tendencies.
  • Duchenne Muscular Dystrophy (DMD): Caused by mutations in the dystrophin gene, leading to reduced or absent dystrophin or abnormal protein, causing muscle degeneration and weakness.
• X-linked Dominant Disorders:
  • Affected males pass the mutation to all daughters but not sons. Affected females pass the condition to half their sons and daughters.
  • Hypophosphatemia: A type of vitamin D-resistant rickets.
  • Alport Syndrome: Associated with progressive hearing loss and kidney disease.

Polygenic Disorders

• Polygenic disorders result from the combined action of multiple genes, unlike monogenic disorders caused by a single gene.
• Examples include hypertension, coronary heart disease, and diabetes, which depend on the simultaneous association of several genes.
• Diabetes Mellitus:
  • Characterized by persistent high blood sugar levels (hyperglycemia).
  • Type 1 Diabetes (T1D): Caused by immunological destruction of pancreatic beta cells, constituting ~10% of cases. Requires lifelong insulin injections.
  • Type 2 Diabetes (T2D): Represents ~90% of cases, caused by impaired insulin secretion from beta cells and peripheral insulin resistance. Insulin is needed to transport glucose into cells for energy and cell function.
• Hypertension:
  • Persistent high blood pressure, a major risk factor for renal, heart, and stroke-related brain issues, and a leading cause of global mortality and morbidity.
  • Blood pressure classifications: Normal (<120/<80 mm Hg), elevated (120-129/<80 mm Hg), stage 1 hypertension (130-139/80-89 mm Hg), stage 2 hypertension (≥140/≥90 mm Hg).
• Coronary Heart Disease (CHD):
  • Caused by narrowing of coronary arteries due to atherosclerosis (fatty material buildup on artery walls), reducing oxygen-rich blood supply to heart muscles (ischemia).
  • Previously called ischemic heart disease due to reduced blood supply to the heart.

Mitochondrial Inheritance and Diseases

• Mitochondria, cytoplasmic organelles, produce energy via ATP through regulated chemical reactions involving enzymes encoded by mitochondrial genes.
• Mutations in mitochondrial genes impair ATP production and cellular function.
• Cells in high-energy organs (brain, heart, kidneys, muscle, liver) contain many mitochondria to meet energy demands.
• In mitochondrial diseases, symptom severity depends on the ratio of normal to abnormal mitochondria in cells; survival is impossible if all mitochondria are defective.
• Mitochondrial DNA is circular, and mitochondria are the only organelles besides the nucleus in animals to contain DNA and genes.
• Sperm contain few mitochondria, so mitochondrial genes are inherited from the mother.
• A father with a mitochondrial gene defect cannot transmit the disease to offspring.