<h5 id="81-chromosomal-abnormalities-and-syndromes">8.1 Chromosomal Abnormalities and Syndromes</h5> <ul> <li> <p>Chromosomal abnormalities can be structural or numerical.</p> </li> <li> <p>Structural abnormalities involve changes in chromosome structure, while numerical abnormalities involve changes in chromosome number.</p> </li> <li> <p>Monosomy (2n-1) is a type of numerical abnormality where one chromosome of the pair is absent, e.g., monosomy of chromosome 1.</p> </li> <li> <p>Trisomy (2n+1) is another type of numerical abnormality where a chromosome is present in three copies, e.g., trisomy of chromosome X.</p> </li> <li> <p>Polyploidy is a condition where the entire set of chromosomes is multiplied, e.g., 69: 23 x 3, 92: 23 x 4. It is commonly found in artificially bred plants used in food, such as bread wheat, cabbages, banana, apple, strawberry, and sugarcane.</p> </li> </ul> <p>======</p> <h5 id="811-structural-chromosomal-abnormalities">8.1.1 Structural chromosomal abnormalities</h5> <ul> <li>Structural chromosomal abnormalities include deletion, duplication, inversion, and translocation.</li> <li>In deletion, a segment of a chromosome breaks away, leading to a shortened chromosome. This can result in conditions like retinoblastoma.</li> <li>Duplication refers to a segment of the chromosome getting repeated, causing a longer chromosome. An example is Charcot-Marie-Tooth disease caused by duplication of genes on chromosome 17.</li> <li>In inversion, a segment of the chromosome breaks away, reverses, and reattaches, maintaining the same chromosome length but reversing gene orientation. An example is RCAD syndrome caused by inversion of a chromosome 17 segment.</li> <li>Translocation involves a segment of a chromosome breaking away and attaching to another chromosome. There are two types: reciprocal translocation (mutual exchange) and Robertsonian translocation (non-mutual exchange), which can result in a decrease in chromosome number.</li> </ul> <p>======</p> <h5 id="812-numerical-chromosomal-abnormalities">8.1.2 Numerical chromosomal abnormalities</h5> <ul> <li>Numerical chromosomal abnormalities often result in various syndromes and diseases.</li> <li>A syndrome is a set of symptoms that consistently occur together, while a disease refers to an abnormal physiological response to internal or external factors.</li> <li>Common syndromes/diseases resulting from numerical chromosomal abnormalities include: <ul> <li>Down syndrome (Trisomy 21)</li> <li>Edwards syndrome (Trisomy 18)</li> <li>Patau syndrome (Trisomy 13)</li> <li>Turner syndrome (Monosomy X)</li> <li>Klinefelter syndrome (XXY)</li> </ul> </li> <li>These syndromes/diseases are characterized by specific symptoms and developmental issues caused by the presence or absence of certain chromosomes.</li> <li>The terms syndrome and disease are often used interchangeably in the context of chromosomal abnormalities.</li> </ul> <p>======</p> <h5 id="1-downs-syndrome">1. Down’s Syndrome</h5> <ul> <li>Down’s Syndrome is a genetic condition, caused by the presence of an extra chromosome 2</li> </ul> <p>======</p> <h5 id="2-klinefelters-syndrome">2. Klinefelter’s syndrome</h5> <ul> <li>Klinefelter’s syndrome is a genetic condition that occurs in approximately 1 out of 1000 newborn males.</li> <li>It is caused by the genotype 47, XXY, where an extra X chromosome is present. This does not come from the father but arises from the inability of the X chromosome to detach itself during meiosis.</li> <li>Clinical symptoms include being unusually tall for their age, reduced facial and body hair, smaller testes, enlarged breasts, and a coarse voice.</li> <li>Diagnosis is often carried out through a Barr body test of a buccal smear. In Klinefelter’s syndrome, one Barr body appears, indicating the presence of an extra X chromosome.</li> <li>Treatment typically involves the use of testosterone to aid in looking more masculine and psychological counseling to control depression leading to aggression.</li> </ul> <p>======</p> <h5 id="3-turners-syndrome">3. Turner’s Syndrome</h5> <ul> <li>Turner Syndrome is a chromosomal disorder affecting 1 in 2,500 newborn girls, caused by the missing X chromosome (karyotype: 45, X). It is not inherited from the mother.</li> <li>The condition is characterized by short stature, webbed neck, small breasts, low-set ears, swollen hands and feet, and underdeveloped ovaries, often resulting in absent menstrual periods.</li> <li>Diagnosis can be made prenatally through amniocentesis or chorionic villus sampling, and at puberty through the first test of Barr body of buccal smear.</li> <li>There is no permanent cure, but growth and ovarian functions can be strengthened by controlled administration of hormones androgen and estrogen.</li> <li>Notable people with Turner Syndrome include fashion designer Isabelle Springmühl, US president George Washington (speculated), model Lauren Foster, actress Linda Hunt, and medical genetics doctor Dr. Catherine Ward Melver.</li> </ul> <p>======</p> <h5 id="82-monogenic-disorders-and-pedigree-mapping-cystic-fibrosis-sickle-cell">8.2 Monogenic Disorders and Pedigree Mapping (Cystic Fibrosis, Sickle Cell</h5> <ul> <li>Monogenic disorders are caused by a single gene error, with over 10,000 estimated to affect millions of individuals worldwide.</li> <li>The nature of the disease and symptoms depend on the functions of the altered gene, and can be inherited according to Mendel’s Laws.</li> <li>Mutations can be spontaneous, and diseases can be caused by a single mutation (sickle cell anemia) or multiple mutations (cystic fibrosis, with over 200 different types).</li> <li>Inherited genetic diseases can be classified into four categories based on the pattern of inheritance: autosomal recessive, autosomal dominant, X-linked recessive, and X-linked dominant.</li> <li>Pedigree analysis, the interpretation of information displayed as a family tree, is used for the diagnosis of inherited genetic diseases. Specific symbols represent different aspects of a pedigree.</li> </ul> <p>======</p> <h5 id="autosomal-recessive-disorder">Autosomal recessive disorder</h5> <ul> <li> <p>Autosomal recessive disorder requires two copies of the mutated gene for the disorder to manifest.</p> </li> <li> <p>An individual with one defective recessive and one normal recessive gene will be a carrier but not develop the disease.</p> </li> <li> <p>Sickle cell anemia, an autosomal recessive disease, is caused by a mutation in the hemoglobin-β gene on chromosome 11, resulting in defective haemoglobin (Hb) that forms rod-like structures in red blood cells.</p> </li> <li> <p>The disease phenotype is determined by genotype: individuals with ss will have sickle cell anemia, while those with SS or Ss will not.</p> </li> <li> <p>Other examples of autosomal recessive disorders include cystic fibrosis, Tay-Sachs disease, and phenylketonuria, each caused by specific gene mutations leading to different health issues.</p> </li> </ul> <p>======</p> <h5 id="autosomal-dominant-disorder">Autosomal dominant disorder</h5> <ul> <li>Autosomal dominant disorder is a type of inheritance where the abnormal allele is dominant and only one copy can cause the disorder.</li> <li>Examples include achondroplasia, a form of dwarfism, and Huntington’s disease, which affects the nervous system.</li> <li>In achondroplasia, normal people have genotype $d / d$, affected individuals with mild disease have $\mathrm{D} / \mathrm{d}$ and severely affected have D/D which is often lethal.</li> <li>X-linked recessive disorder: The affected gene is located on the X chromosome. Mothers (XX) who are carriers pass it on to their sons (XY) who are then affected.</li> <li>Examples of X-linked recessive disorders are Haemophillia and Duchenne Muscular Dystrophy. Haemophilia is a bleeding disorder caused by mutation in coagulation factor VIII gene (type A) or factor IX gene (type B) and Duchenne Muscular Dystrophy (DMD) is caused by mutation of dystrophin gene.</li> </ul> <p>======</p> <h5 id="x-linked-dominant-disorder">X-linked dominant disorder</h5> <ul> <li>X-linked dominant disorder is a type of inheritance where affected males pass on the mutated dominant gene to half of their daughters but to none of their sons.</li> <li>If an affected female is married to an unaffected male, the condition is passed on to half of their sons and daughters.</li> <li>This disorder is characterized by the X chromosome carrying the dominant mutated gene.</li> <li>Females with one copy of the mutated gene are affected, while males with one copy of the gene are often more severely affected and sometimes fatal.</li> <li>Examples of X-linked dominant disorders include hypophosphatemia, a type of vitamin D resistant rickets, and Alport syndrome, which is associated with progressive hearing loss and kidney disease.</li> </ul> <p>======</p> <h5 id="83-polygenic-disorders-hypertension-coronary-heart-disease-and">8.3 Polygenic Disorders (Hypertension, Coronary Heart Disease, and</h5> <ul> <li> <p>A polygenic disorder is caused by the defect or combined action of more than one gene, with hypertension, coronary heart disease, and diabetes being classic examples.</p> </li> <li> <p>Diabetes mellitus is a heterogeneous group of disorders characterized by persistent high blood sugar levels, with Type 1 and Type 2 diabetes being the most common forms. The prevalence of diabetes is predicted to double worldwide from 171 million in 2000 to 366 million in 2030, with a maximum increase in India.</p> </li> <li> <p>Type 1 diabetes is caused by the destruction of the beta cells of the pancreas due to immunological abnormality, while Type 2 diabetes is caused by impaired insulin secretion from beta cells of the pancreas and peripheral insulin resistance.</p> </li> <li> <p>Hypertension, or persistent increase in blood pressure, is a major risk factor for renal, heart, and stroke-related issues, with the current guideline (2017) by the American College of Cardiology mentioning that normal blood pressure is < 120 (systolic)/<80 (diastolic) mm Hg.</p> </li> <li> <p>The Coronary Heart Disease (CHD) is an important cause of morbidity and mortality worldwide, developing due to narrowing of the coronary artery caused by gradual build-up of fatty material on its wall, known as atherosclerosis.</p> </li> </ul> <p>======</p> <h5 id="831-mitochondrial-inheritance-and-diseases">8.3.1 Mitochondrial inheritance and diseases</h5> <ul> <li>Mitochondria are organelles in the cytoplasm of cells that produce energy through ATP. They contain genes that code for critical enzymes involved in ATP production.</li> <li>Mitochondrial diseases are caused by defects or mutations in these genes. The severity of the disease depends on the ratio of normal and abnormal mitochondria in cells.</li> <li>Mitochondrial inheritance only occurs through the mother, as sperm contain very few mitochondria and mitochondrial genes.</li> <li>Mitochondrial diseases can be monogenic, caused by modifications in a single gene, or polygenic, caused by the defect or combined action of more than one gene.</li> <li>Structural chromosomal abnormalities include deletion, duplication, inversion, and translocation, which can lead to various syndromes such as Down, Klinefelter, and Turner syndromes.</li> </ul> <p>======</p>