الجليكوجين والأمراض الوراثية

Genetic Diseases

• Genetic diseases are conditions caused by abnormalities in genes.
• There are approximately 4,000 known inherited human diseases.
• Genetic disorders can be caused by mutations in single genes (Mendelian disorders) or by complex interplay of multiple genes and environmental factors (multifactorial inheritance).

Hereditary Disorders

• Hereditary disorders are passed from parent to offspring.
• They are transmitted through gametes (sperm and egg) during reproduction.
• Hereditary disorders are familial, meaning they often run in families.

Congenital Diseases

• Congenital diseases are present at birth.
• Not all congenital diseases are genetic; some can be caused by environmental factors during pregnancy.
• Congenital syphilis is an example of a congenital disease that is not genetic.

Mutations

• Mutations are permanent changes in DNA.
• Germ cell mutations are passed to offspring, leading to inherited diseases.
• Somatic cell mutations are not inherited but can lead to cancers and some congenital malformations.

Types of Mutations

• Point mutation: A single nucleotide base is substituted by a different base, causing a change in one amino acid in the protein product.
  • Sickle cell anemia is an example, where a nucleotide triplet encoding glutamic acid is changed to one encoding valine.
  • This type of mutation is called missense mutation.
• Frameshift mutation: An insertion or deletion of one or two base pairs alters the reading frame of the DNA strand, affecting all subsequent codons.
  • Three-base deletion in the cystic fibrosis CF allele, results in the loss of one amino acid. This is not a frameshift mutation as the deletion is a multiple of three.
• Four-base insertion: In the hexosaminidase A gene, leading to a frameshift mutation, a major cause of Tay-Sachs disease.
• Single-base deletion: At the ABO glycosyltransferase locus, leading to a frameshift mutation responsible for the O allele.
• Trinucleotide repeat mutations: Characterised by the amplification of a sequence of three nucleotides, example fragile X syndrome which has 250-4000 repeats of the CGG sequence.

Autosomal Dominant Disorders

• At least one parent of an affected individual is usually affected.
• Males and females are equally affected.
• If an affected person marries an unaffected one, each child has a 50% chance of inheriting the disease.
• Examples include Marfan syndrome, hypercholesterolemia, polycystic kidney disease, hereditary spherocytosis, familial polyposis coli.

Autosomal Recessive Disorders

• Manifested in homozygous state where both alleles at a given locus are mutant.
• Affected individuals tend to have unaffected parents who carry a single copy of the mutated gene.
• Siblings of an affected individual have a 25% risk for each birth.
• Examples include sickle cell anemia, thalassemia, glycogen storage disease, cystic fibrosis, phenylketonuria, Wilson disease.

X-linked Disorders

• Most X-linked diseases are recessive.
• Affected males cannot transmit the condition to their sons, but all their daughters are carriers.
• Sons of heterozygous mothers have a 50% chance of inheriting the disease.
• Examples include hemophilia A and B, glucose-6-phosphate dehydrogenase deficiency (G6PD deficiency), agammaglobulinemia, Duchenne muscular dystrophy.

Diseases Caused by Mutations in Structural Proteins

• Marfan syndrome : An autosomal dominant disorder of connective tissue affecting fibrillin.
• Affected individuals have skeletal abnormalities (e.g., long limbs, high arched palate), eye problems (e.g., lens dislocation), and cardiovascular issues (e.g., aortic aneurysms).

Diseases Caused by Mutations in Receptor Proteins

• Familial hypercholesterolemia is an autosomal dominant disorder.
• Heterozygotes have elevated plasma cholesterol.
• Homozygotes have severe elevations, xanthoma in childhood, and myocardial infarction in their teens and twenties.

Diseases Caused by Mutations in Enzymes

• Phenylketonuria (PKU) is an autosomal recessive disorder.
• Affected individuals lack the enzyme phenylalanine hydroxylase, resulting in the accumulation of phenylalanine and its toxic metabolites.
• Symptoms include mental retardation, seizures, a distinctive musty odor, and a light-colored skin and hair.
• Can be treated with a strict diet low in phenylalanine.

Glycogen Storage Disorders

• Inherited deficiencies in enzymes involved in glycogen synthesis or degradation.
• Lead to excessive glycogen accumulation or abnormal form of glycogen in various tissues, which harms the body.
• Examples include hepatic, myopathic, and other forms.

Diseases Caused by Mutation in Protein that Regulate Cell Growth

• Prooncogenes and cancer suppressor genes regulate cell growth.
• Mutations can lead to tumor formation.

Numerical Abnormalities

• A normal chromosome count of humans is 46 (2n = 46).
• An exact multiple of the haploid number (n) is termed euploid.
• Non-exact multiples of n are termed aneuploid (abnormal number of chromosomes).
• Non-disjunction is a main cause of aneuploidy.

Structural Abnormalities

• Involve chromosome breakage and rearrangement.
• Examples include translocation (e.g., Philadelphia chromosome), isochromosomes (e.g., loss of one arm of a chromosome and duplication of the other arm), deletion, and inversion.

Diagnosis of Genetic Diseases

• Karyotype analysis and Fluorescence in Situ Hybridization (FISH) are used to examine chromosomes, while polymerase chain reaction (PCR) is used to study genes' sequences.
• Prenatal testing using methods like amniocentesis or chorionic villus sampling allows looking for genetic abnormalities before birth.

Mitochondrial Genes

• Mitochondria contain genes encoding enzymes for oxidative phosphorylation.
• Inheritance of mitochondrial genes is typically maternal (through the egg).
• Leber's optic neuropathy is an example of a rare disease linked to mitochondrial genes.

Genomic Imprinting

• Genomic imprinting involves different expressions of maternal and paternal genes.
• Diseases like Prader-Willi and Angelman syndromes show different clinical features based on which parent's gene is imprinted.

Genetic Counseling

• Genetic counseling helps individuals make informed decisions about childbearing options.

Prenatal and Postnatal Genetic Analysis

• Prenatal genetic analysis is used on pregnant patients who are at high risk for a child with genetic abnormalities.
• Postnatal genetic analysis looks for chromosomal abnormalities and defects, multiple or unexplained birth defects, unexplained mental retardation etc.

Detecting Birth Defects

• Methods like amniocentesis, chronic villus sampling, ultrasound sonography, and maternal blood test help detect birth defects.

Gene Therapy

• Gene therapy alters somatic cells to treat disease.
• Researchers inject genes, which then produce chemicals to treat the defective genes.

Steps in Gene Therapy In Utero

• The steps involve injecting genes using a vector, often a virus.

تتناول هذه الاختبارات مواضيع حول تخزين الجليكوجين والأمراض المرتبطة به، بما في ذلك داء بومبي. كما تستكشف تأثير الطفرات الجينية وكيفية تأثيرها على الصفات الوراثية. اختبر معرفتك في علم الوراثة وعلم البيولوجيا الخلوية.