Human Diseases: A Systemic Approach Study Notes

Human Diseases: A Systemic Approach, 8/e

Chapter Overview

  • Heredity and Disease

Objectives

  • Describe DNA's composition and its role in heredity

    • DNA is the primary carrier of genetic information.

    • It determines biological inheritance.

  • Explain the transmission of hereditary diseases

    • Hereditary diseases can be passed from parents to offspring through genes.

  • Understand how diseases are reflected in abnormal karyotype and chromosome structure

    • Karyotype analysis helps identify chromosomal abnormalities linked to diseases.

  • Compare and contrast congenital diseases and genetic disorders

    • Congenital diseases are present at birth, while genetic disorders are related to abnormalities in the genes.

  • Understand how gene therapy might be used to treat genetic diseases and disorders

    • Gene therapy involves altering the genes inside the body's cells to treat or stop disease.

DNA and Chromosomes

  • DNA is the Cell's Master Code

    • Deoxyribonucleic Acid (DNA): The molecule that carries the genetic instructions for life.

    • Genes: Segments of DNA that contain the instructions for the development and functioning of an organism.

  • Chromosomes

    • Chromosome Composition:

    • Autosomes: 22 pairs of chromosomes that are not involved in sex determination.

    • Sex Chromosomes: 2 chromosomes (X and Y) that determine an individual’s sex.

    • Karyotype: The number and appearance of chromosomes in the nucleus of a cell.

  • Cell Division

    • Meiosis: A type of cell division that produces gametes with half the number of chromosomes.

Stages of Mitosis

  1. Prophase:

    • Chromosomes condense and form sister chromatids.

    • Centromeres join sister chromatids.

    • The nuclear envelope dissolves.

    • Centrioles migrate to opposite poles of the cell.

  2. Prometaphase:

    • Centrosomes move to opposite ends and develop spindle fibers.

    • Chromosomes attach to spindle fibers via kinetochores and align along the equator.

  3. Metaphase:

    • Chromosomes are aligned along the equator.

    • Sister chromatids are attached to spindle fibers from opposite poles.

  4. Anaphase:

    • Chromatids split at the centromere and migrate to opposite ends.

  5. Telophase:

    • New chromosomes gather at opposite poles.

    • Nuclear envelope reforms.

    • Result: Two identical daughter cells.

The Human Genome and Disease

  • Genome: The complete set of genes or genetic material present in a cell or organism.

  • Sequence of DNA: The order of nucleotides in DNA that determines hereditary characteristics.

  • National Human Genome Research Institute: An organization that conducts research on DNA and the human genome.

Meiosis

  • Definition: A specialized type of cell division that occurs in germ cells to produce gametes (sperm and egg).

  • Process:

    • Involves two rounds of division leading to four haploid cells.

    • Each daughter cell has one copy of each chromosome, which is essential for sexual reproduction.

Genes and Inheritance

  • Locus: The specific location of a gene on a chromosome.

  • Alleles: Different forms of a gene.

    • Homozygous: A pair of identical alleles (e.g., two alleles for blue eyes).

    • Heterozygous: Two different alleles (e.g., one allele for blue eyes and one for brown eyes).

  • Dominance:

    • A gene is dominant if its effects are evident in the presence of a different allele.

    • Recessive: An allele that is only expressed when both alleles are identical.

  • Genotype vs. Phenotype:

    • Genotype: The genetic makeup (e.g., genotype for brown eyes could be BB or Bb).

    • Phenotype: The physical expression of the genotype (e.g., brown eyes).

Transmission of Hereditary Diseases

  • Autosomal Dominant Disorders:

    • Every child of an affected individual has a 50% chance of being affected.

    • Examples include:

    • Huntington's Disease

    • Polydactyly

    • Achondroplasia

    • Marfan Syndrome

    • Familial Hypercholesterolemia

  • Autosomal Recessive Disorders:

    • There is a 25% chance for an affected child and a 50% chance of having a carrier child.

    • Examples include:

    • Cystic Fibrosis

    • Hemochromatosis

    • Phenylketonuria (PKU)

    • Galactosemia

    • Sickle cell anemia

    • Tay-Sachs

    • Albinism

Specific Genetic Disorders

Achondroplasia

  1. Definition: Autosomal dominant trait leading to short limb dwarfism.

  2. Occurence: About 80% of cases are due to new mutations.

  3. Pathophysiology: Faulty cartilage growth and bone conversion at the epiphyses, leading to shortened long bones.

  4. Physical Characteristics: Average torso with prominent lower back curvature (lordosis), large head, and prominent forehead.

  5. Health Problems: Possible intermittent breathing difficulties and recurrent ear infections.

Phenylketonuria (PKU)

  1. Definition: Recessive trait characterized by a deficiency of phenylalanine hydroxylase enzyme.

  2. Metabolic Consequence: Phenylalanine cannot be converted into tyrosine, leading to toxic accumulation.

  3. Impact: Results in mental deficiency if untreated.

  4. Diagnosis: Blood test shortly after birth.

  5. Treatment: Restriction of phenylalanine in diet.

Hemochromatosis

  1. Definition: An autosomal recessive disorder with excessive iron absorption and storage.

  2. Symptoms: Bronze-skinned appearance, diabetes from tissue damage, cirrhosis of the liver, and heart failure.

  3. Treatment: Recurring phlebotomy (blood drawing) and iron binding medication.

Tay-Sachs Disease

  1. Definition: A genetic recessive disorder primarily found among Eastern European Jewish populations.

  2. Pathophysiology: Absence of Hexose Aminidase A allows ganglioside accumulation in the brain.

  3. Symptoms: Gradual physical and mental deterioration, cherry-red spot in the retina.

  4. Prognosis: Death typically occurs before age four.

  5. Carrier Detection: Blood tests for low Hexose Aminidase A levels.

Sickle Cell Anemia

  1. Genetic Basis: Both alleles for hemoglobin produce hemoglobin S.

  2. Condition Trigger: Reduced oxygen environments lead to changes in red blood cell shape (sickle shape).

  3. Consequences: Diminished blood flow, damaging heart, liver, spleen, bones, etc.

  4. Statistics: About 10% of African Americans are carriers of the sickle cell trait.

Cystic Fibrosis

  1. Definition: An autosomal recessive condition caused by abnormalities in sodium chloride transport across cell membranes.

  2. Physical Impact: Thickened mucus secretions lead to lung and pancreatic dysfunction.

  3. Diagnosis: Conducted using a sweat test.

  4. Lifelong Implications: Development of pneumoniae and slow growth despite high appetite.

  5. Average Lifespan: Approx. 32 years.

Hemophilia

  1. Definition: A genetic bleeding disorder linked to the X chromosome resulting in factor VIII deficiency.

  2. Symptoms: Characterized by bleeding into joints.

  3. Genetic Basis: Males carry X-linked traits; hemizygosity means a male will express the disorder if the X carries the hemophilia gene.

Sex-Linked Inheritance

  • Examples include:

    • Duchenne's Muscular Dystrophy

    • Color Blindness

    • Fragile X Syndrome

Fragile X Syndrome

  1. Definition: A genetic syndrome with greater prevalence in males than females.

  2. Mental Health Impact: Many males and about 30% of females with this syndrome are mentally deficient.

  3. Physical Characteristics: The X chromosome has a constricted neck due to excessive CGG repeats; features include long faces, large ears, and prominent jaws.

Transmission of Sex-Linked Disorders

  • Disorders that follow sex-linked inheritance can be passed from carrier mothers to male offspring.

Familial Diseases

  • Familial diseases do not result from a single gene but from interactions between several genes and environmental factors, indicating a multifactorial inheritance pattern.

Abnormal Chromosomal Diseases

  • Down Syndrome (Trisomy 21):

    • Characterized by unique appearance, intellectual disability, and shortened lifespan.

    • Incidence: Approximately 1 in 691 births, with varying risk based on maternal age.

    • Common Features: Upward slant to eyes, low muscle tone, small stature, and palm crease.

  • Sex Anomalies:

    • Turner's Syndrome: Characterized by a single X chromosome leading to female phenotypes with developmental issues.

    • Delayed puberty, short stature, infertility, heart defects, and learning disabilities.

    • Klinefelter's Syndrome: Characterized by an XXY chromosome leading to male phenotypes with various reproductive and physical characteristics like sparse facial hair and learning disabilities.

Genetic Counseling and Diagnosis

  • Methods for Genetic Disease Diagnosis:

    • Amniocentesis: A procedure to sample amniotic fluid for genetic analysis.

    • Chorionic Villus Sampling: A technique to sample tissue from the placenta for chromosomal analysis.

  • Gene Therapy: A treatment approach attempting to amend defective genes responsible for disease development.

Congenital Disorders

  • Examples include:

    • Congenital rubella

    • Cerebral palsy

    • Hydrocephalus

    • Spina bifida

    • Congenital heart disease

    • Congenital intestine disorders

    • Cleft lip and palate