Patho Chapter 4 Study Guide

Microscopic Studies of Cells

• In the 19th century, studies indicated that the nucleus contains mechanisms of inheritance.

• Chromatin observed in nondividing cells, which condenses to form chromosomes during cell division.

• Chromosomes contain genes, which are the basic units of inheritance, composed of DNA and proteins.

Genetics and Human Disease

• Approximately 20,000 to 25,000 human genes identified.

• Errors in genes can lead to genetic diseases; over 23,000 individual human genetic traits cataloged.

• One-third of pediatric inpatients suffer from genetic diseases, with common adult diseases (hypertension, diabetes, cancer) also linked to genetic factors.

• Genetic testing and gene therapy are advancing to guide diagnosis and treatment of these diseases.

Genetic Testing

• Identifies several thousand diseases with known genetic causes.

• Carrier screening can determine whether individuals carry recessive disease alleles (e.g., cystic fibrosis, Tay-Sachs).

• Prenatal diagnosis methods include:

  • Amniocentesis: Withdrawal of amniotic fluid to analyze fetal cells.

  • Chorionic Villus Sampling (CVS): Sampling of chorionic tissue, performed earlier than amniocentesis.

  • Preimplantation Genetic Diagnosis (PGD): Testing of embryos created through IVF.

  • Fetal DNA analysis in maternal blood: Non-invasive testing available as early as 6 weeks of gestation.

• Presymptomatic testing available for hereditary diseases (e.g., familial breast or colon cancer).

• Genetic testing helps predict drug efficacy and sensitivity to avoid adverse reactions (e.g., HIV treatment with Abacavir).

Limitations of Genetic Testing

• Genetic testing reveals mutations but many diseases exhibit incomplete penetrance (e.g., BRCA mutations linked to breast cancer).

• Negative test results do not rule out the possibility of disease.

Gene Therapy

• Gene therapy aims to correct mutations in DNA to treat diseases.

• Includes somatic cell gene therapy; challenges include immune response and safe delivery of genes using vectors (often modified viruses).

• Successful gene therapy treatments have reversed symptoms in conditions like severe combined immunodeficiency (SCID) and hemophilia B.

• Ongoing research aims to develop safe gene therapies for more diseases.

DNA Structure and Function

• DNA composed of nitrogenous bases (A, T, C, G) forming a double helix.

• Codons consist of three base sequences that code for amino acids; 64 possible codons in total.

• DNA replication involves unwinding double helix and complementary base pairing via DNA polymerase, which also has proofreading capability to ensure accuracy.

Mutations

• A mutation is an inherited alteration of genetic material.

• Types of mutations include:

  • Base Pair Substitution: Replacement of one base pair with another.

  • Missense Mutation: Results in a different amino acid.

  • Nonsense Mutation: Introduces a premature stop codon.

  • Frameshift Mutation: Involves insertion or deletion that shifts the reading frame.

• Mutagens can increase mutation frequency (e.g., radiation, chemicals).

Gene Expression and Protein Synthesis

• RNA is synthesized from DNA in a process called transcription, producing mRNA.

• mRNA undergoes splicing; introns are removed, exons rejoined.

• Translation of mRNA directs polypeptide synthesis, involving tRNA and ribosomes.

• Noncoding RNAs (like miRNAs and lncRNAs) play regulatory roles in gene expression.

Chromosomes and Abnormalities

• Somatic cells are diploid (46 chromosomes), while gametes are haploid (23 chromosomes).

• Chromosome abnormalities lead to major genetic diseases and are the leading known cause of intellectual disability.

• Types of chromosome abnormalities include aneuploidy (e.g., trisomy, monosomy) and structural abnormalities (e.g., deletions, duplications).

• Down syndrome (trisomy 21) is a commonly recognized chromosomal disorder resulting from nondisjunction.

Modes of Inheritance

• Modes of inheritance identified include autosomal dominant, autosomal recessive, and X-linked conditions.

• Pedigree charts are crucial for tracking genetic diseases across generations.

• Autosomal Dominant Traits: Equal occurrence in sexes, no skipping generations, ~50% recurrence risk.

• Autosomal Recessive Traits: Both sexes affected equally, often seen in siblings, ~25% recurrence risk.

• X-Linked Recessive Traits: More common in males, skipped generations possible, can transmit through carrier females.

Linkage Analysis

• Genes on the same chromosome may be linked and inherited together due to proximity.

• Crossing over during meiosis can lead to recombination, and frequencies of recombination give insights into gene mapping.

• Genetic testing facilitates pinpointing disease-causing mutations and enhances genetic diagnosis.

Summary Points

1. Genes located on chromosomes; composed of DNA and specify proteins.

2. Mutation presence can alter genetic disease risk; various modes of inheritance exist.

3. Gene therapy is evolving to correct genetic disorders.

4. Genetic testing is valuable for diagnosis, treatment, and understanding disease inheritance patterns.