Genes and Genetic Disease
Chapter 4: Genes and Genetic Disease
Chapter Objectives
Describe the structure and function of deoxyribonucleic acid (DNA) in molecular inheritance.
Discuss the processes of transcription and translation and the roles of messenger RNA (mRNA) and transfer RNA (tRNA).
Describe the normal karyotype.
Differentiate between genotype and phenotype.
Define and provide examples for key genetic terms: progeny, chromosomes, gene, allele, gamete, homozygous, heterozygous, dominant traits, recessive traits, pedigree chart, penetrance, and expressivity.
List the cause and possible outcomes for mutations: base-pair substitution, frameshift substitution, spontaneous mutation, and mutational hotspots.
Define and provide examples for chromosome terms: euploid, haploid, diploid, polyploidy, aneuploid, trisomy, partial trisomy, monosomy, disjunction, nondisjunction, and chromosomal mosaics.
Describe deviations in normal chromosome structure: deletion, duplication, inversion, translocation, and fragile sites.
Define and describe inheritance elements: autosomal, sex-linked, carrier, dominant, and recessive.
Evaluate pedigree charts for single-gene genetic disease inheritance patterns.
Evaluate recurrence or occurrence risk for single-gene inheritance patterns given parental genotypes or using a Punnett square.
Describe genetic and clinical abnormalities for: Down syndrome, Turner syndrome, Klinefelter syndrome, cri du chat syndrome, Huntington disease, cystic fibrosis, neurofibromatosis, hemophilia, and Duchenne muscular dystrophy.
Compare and contrast somatic cell and in situ hybridization.
Discuss the purposes of gene mapping.
DNA, RNA, and Proteins: Heredity at the Molecular Level
Chromosomes and Genes
Chromosomes contain genes.
Genes are the basic unit of inheritance, composed of DNA.
DNA Structure
DNA is a double helix structure.
DNA subunit (nucleotide) contains:
One pentose sugar (deoxyribose).
One phosphate group.
One nitrogenous base:
Cytosine (C)
Thymine (T)
Adenine (A)
Guanine (G)
DNA as the Genetic Code
DNA provides the code for all body proteins.
Proteins are composed of one or more polypeptides.
Polypeptides are composed of 20 amino acids.
A sequence of three bases (codons) directs the production of specific amino acids.
Termination and nonsense codons signal the stop of protein production.
Replication of DNA
The DNA strand untwists and unzips.
A single strand acts as a template.
DNA polymerase pairs complementary bases:
Adenine pairs with thymine (A-T).
Cytosine pairs with guanine (C-G).
DNA polymerase adds new nucleotides and performs proofreading to ensure accurate replication.
Each new DNA molecule consists of one original (template) strand and one newly synthesized strand, a process known as semiconservative replication.
RNA Structure and Function
RNA (Ribonucleic Acid) is a single-stranded nucleic acid.
RNA subunit contains:
One pentose sugar (ribose).
One phosphate group.
One nitrogenous base:
Cytosine (C)
Uracil (U) - replaces Thymine (T) found in DNA
Adenine (A)
Guanine (G)
Different types of RNA play crucial roles in protein synthesis:
Messenger RNA (mRNA): Carries genetic information from DNA in the nucleus to the ribosomes in the cytoplasm.
Transfer RNA (tRNA): Delivers specific amino acids to the ribosome during protein synthesis, matching them to codons on the mRNA.
Ribosomal RNA (rRNA): A structural component of ribosomes, where protein synthesis occurs.
Transcription: DNA to mRNA
Transcription is the process by which genetic information from DNA is copied into mRNA.
Occurs in the nucleus.
Steps:
Initiation: RNA polymerase binds to a promoter region on the DNA, unwinding the double helix.
Elongation: RNA polymerase synthesizes an mRNA strand by adding complementary RNA nucleotides to the DNA template strand.
Adenine (A) in DNA pairs with Uracil (U) in mRNA.
Thymine (T) in DNA pairs with Adenine (A) in mRNA.
Cytosine (C) in DNA pairs with Guanine (G) in mRNA.
Guanine (G) in DNA pairs with Cytosine (C) in mRNA.
Termination: RNA polymerase reaches a terminator sequence, and the mRNA strand is released.
Post-transcriptional modification: Pre-mRNA undergoes processing:
Splicing: Introns (non-coding regions) are removed, and exons (coding regions) are joined together.
A 5' cap and a poly-(A) tail are added to protect the mRNA and aid in translation.
Translation: mRNA to Protein
Translation is the process where mRNA sequence is used to synthesize a protein.
Occurs in the cytoplasm, on ribosomes.
Steps:
Initiation: The ribosome binds to the mRNA at the start codon (typically AUG), and the first tRNA carrying methionine binds to the start codon.
Elongation: tRNAs, each carrying a specific amino acid, bind to successive codons on the mRNA.
The ribosome catalyzes the formation of peptide bonds between adjacent amino acids.
The ribosome moves along the mRNA, reading codons one by one.
Termination: The ribosome encounters a stop codon (UAA, UAG, or UGA), for which there is no corresponding tRNA.
Release factors bind to the stop codon, causing the polypeptide chain to be released from the ribosome.
The ribosome complex disassembles.
The newly synthesized polypeptide then folds into its specific three-dimensional structure, often with the help of chaperone proteins, to become a functional protein.
Chromosomal Basis of Inheritance
Normal Karyotype
A karyotype is an organized profile of a person's chromosomes, arranged in homologous pairs.
Human somatic cells normally contain 46 chromosomes arranged in 23 pairs.
22 pairs are autosomes (non-sex chromosomes).
1 pair consists of sex chromosomes, determining genetic sex (e.g., XX for female, XY for male).
Chromosomes are typically visualized during metaphase of mitosis, when they are condensed and easily stained.
Karyotyping is used to detect chromosomal abnormalities, such as changes