Concise Genetics and Cell Function Notes

Genetic Control of Cell Function

• Genetic information stored in DNA directs cell function, appearance, response to the environment, and inheritance.
• Completion of the Human Genome Project in 2003 and subsequent innovations have expanded the understanding of genetics in disease.
• DNA's stable structure allows it to survive cell division, gamete formation, fertilization, and mitotic divisions.
• RNA is involved in the synthesis of cellular proteins using information transcribed from DNA.
• Proteins, encoded by genes, constitute cellular structures and perform biological functions and are targets for many drugs.

DNA Structure and Function

• DNA is a double-stranded, helical structure composed of nucleotides.
• Nucleotides consist of phosphoric acid, deoxyribose (a five-carbon sugar), and a nitrogenous base (adenine, guanine, cytosine, or thymine).
• Base pairing rules: Adenine (A) pairs with Thymine (T), and Guanine (G) pairs with Cytosine (C).
• DNA replicates semiconservatively, with each new DNA molecule consisting of one old strand and one new strand.
• DNA is packaged into chromosomes with the help of proteins like histones, forming a tightly coiled structure called chromatin.
• Chromatin remodeling, such as acetylation (gene activation) and methylation (gene inactivation), affects gene accessibility.

DNA Repair and Genetic Variability

• Mutations are errors in DNA replication, which can occur spontaneously or due to environmental factors.
• DNA repair mechanisms, involving enzymes like endonucleases and DNA polymerase, correct most defects.
• Variations in gene sequence (0.01%) account for individual differences; these variations are called polymorphisms.

From Genes to Proteins: RNA

• RNA assembles amino acids into proteins through translation.
• RNA differs from DNA by being single-stranded, containing ribose instead of deoxyribose, and using uracil (U) instead of thymine (T).
• Three types of RNA: messenger RNA (mRNA), ribosomal RNA (rRNA), and transfer RNA (tRNA).
• mRNA carries instructions for protein synthesis from DNA.
• rRNA is part of the ribosome and translates instructions for protein synthesis.
• tRNA delivers appropriate amino acids to the ribosome.

Transcription and Translation

• Transcription: RNA is synthesized from a DNA template in the nucleus, using RNA polymerase.
• The promoter region, including the TATA box, is crucial for transcription initiation.
• Splicing: Introns (non-coding regions) are removed, and exons (coding regions) are retained in mRNA.
• Translation: mRNA is used to synthesize a protein in the cytoplasm.
• tRNA delivers amino acids to the ribosome according to the mRNA codon sequence.

Regulation of Gene Expression

• Gene expression is the degree to which a gene is actively transcribed.
• Induction increases gene expression, while repression reduces it.
• Transcription factors regulate gene transcription by binding to specific DNA regions.

Chromosomes

• DNA is organized into chromosomes. Human somatic cells have 23 pairs.
• 22 pairs are autosomes, and the 23rd pair are sex chromosomes (XX for females, XY for males).
• Mitosis duplicates somatic cells, each with 46 chromosomes (23 pairs).
• Meiosis replicates germ cells, resulting in gametes with 23 single chromosomes.
• A karyotype is a photographic arrangement of chromosomes.

Chromosome Structure

• Chromosomes are classified based on centromere position: metacentric, submetacentric, or acrocentric.
• Chromosome arms are designated as p (short arm) and q (long arm).
• Banding patterns are used to describe gene positions on a chromosome.

Patterns of Inheritance

• Genotype is the genetic information, while phenotype is the observable trait.
• Alleles are alternate forms of a gene at the same locus.
• Single-gene traits follow Mendelian laws.
• Polygenic inheritance involves multiple genes.
• Multifactorial inheritance includes both multiple genes and environmental factors.
• Genetic imprinting: parental genomes do not contribute equally, affecting offspring development.

Mendel's Laws

• Mendel's laws describe single-gene inheritance.
• Dominant traits appear in homozygous or heterozygous pairings.
• Recessive traits appear only in homozygous pairings.
• Heterozygous individuals carrying a recessive trait are called carriers.
• A pedigree is a graphic method for tracing inherited traits in a family.

Gene Technology

• Genetic mapping assigns genes to specific loci.
• The Human Genome Project identified all genes in the human genome.
• Linkage studies track the inheritance of genes.
• Hybridization studies involve somatic cell and in situ hybridization.

Genetic Mapping Methods

• Family linkage studies: Genes close together on the same chromosome are likely to be inherited together.
• Hybridization Studies: Somatic cell hybridization fuses cells from different species to map genes to specific chromosomes; In situ hybridization uses tagged DNA or RNA probes to detect gene locations.

Haplotype Mapping

• The International HapMap Project developed a haplotype map of DNA sequence variations.
• Single nucleotide polymorphisms (SNPs) are sites where people differ at a single DNA base.
• A haplotype consists of closely linked SNPs passed as a block from one generation to another.

Recombinant DNA Technology and Gene Therapy

• Recombinant DNA combines DNA molecules not found together in nature.
• Restriction enzymes cut DNA at specific sequences for gene cloning.
• Gene isolation and cloning produce copies of modified DNA.
• DNA fingerprinting uses recombinant DNA technology for forensic analysis.
• Gene therapy: Transferred genes can replace defective genes or inhibit deleterious genes; CRISPR-Cas9 technology edits genes by cutting out and replacing sections of the genome.

RNA Interference Technology

• RNA interference (RNAi) suppresses gene expression by using small interfering RNA.
• RNAi is used to target genes for therapeutic purposes.
• Reverse genomics infers genes function through silencing its expression using RNAi.

Considerations

• Geriatric: Single-gene mutations influence aging; telomere shortening contributes to aging.
• Pediatric: Chromosomal anomalies cause cognitive impairment and birth defects; newborn screening is used for inborn errors of metabolism; family pedigrees identify genetic disorders.