Introduction to Genetics and Pediatric Diseases

Introduction to Genetics and Pediatric Diseases

• Genetics is the study of heredity, a biological process where parents pass genes to their offspring.
• DNA is the fundamental molecule that contains genetic information in an organism. DNA replicates during reproduction and passes from parent to offspring.
• Genes are located on chromosomes, and both chromosomes and genes are made of DNA.
• Genes act as blueprints for heredity and are composed of hundreds to thousands of DNA bases.
• Genes primarily function by producing proteins.
• Most genes occur in pairs, and members of a gene pair can differ from one another.
• The human genome has 3 billion base pairs of DNA; less than 1.5% encodes proteins.
• About 5% of the genome contains regulatory elements
• About half of the total DNA length is single-copy or unique DNA; the rest is repetitive DNA (e.g., Alu is 10%, and LINE is 20%).
• Most of the ~25,000 genes are located in single-copy DNA.
• Repetitive DNA is involved in chromosome structure and contributes to variation between individuals.

Lecture Outline

• Genes, genome, and chromosomes
• The central dogma of molecular genetics
• Genetics and disease
• Diagnosis of genetic diseases
• Treatment of genetic diseases
• Genetic testing and screening
• Genetic counseling

Basic Facts About Genes and Chromosomes

• Genes are located on chromosomes.
• Chromosomes and genes are made of DNA.
• Genes hold the genetic blueprint for heredity.
• Genes are constructed of hundreds to thousands of DNA bases.
• Genes mostly create proteins.
• Genes usually occur in pairs.
• Members of a gene pair can differ from one another.

The Human Genome

• The human genome contains 3 billion base pairs of DNA.
• Less than 1.5% of DNA encodes proteins.
• Approximately 5% of the genome is believed to contain regulatory elements.
• Only about half the linear length of the genome comprises single-copy/unique DNA.
• The remaining portion consists of several classes of repetitive DNA, such as Alu (10%) and LINE (20%).
• Most genes reside within the single-copy DNA section.
• Repetitive DNA maintains chromosome structure and contributes to differences among individuals.

Inside the Cell (Structure)

• Cells contain a nucleus.
• The nucleus contains chromosomes.
• Chromosomes are made of DNA.
• Genes are segments of DNA.

Chromosomes and Inheritance

• Humans have 46 chromosomes organized in pairs (autosomes and allosomes).
• Autosomes are body chromosomes, and allosomes are sex chromosomes (XY).

Structure of DNA

• DNA is a double helix.
• DNA is organized into nucleosomes ("beads on a string").
• Nucleosomes coil into a solenoid structure;
• The solenoid fibers loop to form an interphase chromosome within the nucleus.

Central Dogma of Molecular Biology

• DNA replicates to create more DNA.
• DNA transcribes to produce RNA.
• RNA is translated to provide instructions for protein production.
• The process flows from DNA to RNA to protein.

Parts of a Gene

• Regulatory elements (enhancers, promoters) regulate gene expression; determine how much, in what tissue, and when a gene is expressed.
• Protein-coding sequence translates to a protein product.

Genes and Disease

• Mutations can cause changes in genes, leading to health problems.
• Single-gene disorders show varying inheritance patterns (autosomal dominant, autosomal recessive, X-linked dominant, X-linked recessive).

Cancer Genetics and Genomics

• Cancer arises from an imbalance between cellular proliferation and cellular attrition.
• Cancer affects over one-third of the population and accounts for a significant portion of deaths worldwide.

Genes in Which Mutations Cause Cancer

• Oncogenes stimulate uncontrolled cell growth or inhibit apoptosis (programmed cell death).
• Tumor-suppressor genes (TSGs) regulate cell-cycle checkpoints and mediate programmed cell death.
• Caretaker genes maintain genomic integrity by detecting and repairing mutations, along with ensuring proper chromosome division during mitosis.

What is Inheritance?

• All living organisms inherit traits from their parents.
• Genetics is the scientific study of heredity.

Vocabulary to Know

• Trait: A characteristic, like eye color.
• Gene: A section of DNA determining a trait.
• Hybrid: Offspring of parents with different traits.
• Gamete: A reproductive cell (e.g., sperm and egg).
• Allele: Different forms of a gene.
• Dominant allele: A trait expressed with only one copy.
• Recessive allele: A trait expressed only when no dominant allele is present
• Genotype: The combination of alleles, what the genes say.
• Phenotype: The observable trait, like widow's peak.
• Codominance: Both alleles contribute to the phenotype.
• Multiple alleles: Involve more than two allele possibilities, such as blood type.
• Polygenic traits: Traits determined by more than one gene, like skin color.

Allele Combinations

• Homozygous: Both alleles are the same (WW or ww).
• Heterozygous: Alleles are different (Ww)

Genotype and Phenotype

• Genotype: The combination of alleles an organism has.
• Phenotype: The observable trait.

Codominance

• Both alleles contribute to the phenotype.

Multiple Alleles

• More than two possibilities for alleles, like blood type.

Polygenic Traits

• Traits determined by more than one gene.

Classification of Genetic Disorders

• Single-gene disorders
• Chromosomal disorders
• Multifactorial disorders

Variation in Chromosomal Structure

• Deletion
• Duplication
• Translocation

Human Chromosome Abnormalities

• Variations in the number of chromosomes, or variations in their structure, can lead to health issues.

Aneuploidy

• A term for variations in the number of chromosomes; not an exact multiple of the standard number (n) of chromosomes.
• Types such as Monosomy, Trisomy, Tetrasomy, Double trisomy, and Nullosomy.

Euploidy/Polyploidy

• An increase in chromosome number due to complete chromosome sets.
• Types include Monoploid, Diploid, Triploid, Tetraploid, Autotetraploid, and Polyploid.

Sex Chromosome Anomalies

• Turner's syndrome (45,X0)
• Klinefelter's syndrome (47,XXY)
• Jacob's syndrome (47,XYY)
• Triple X syndrome (47,XXX)

Structural Sex Chromosome Anomalies

• Y-linked diseases (very rare)
• X-linked diseases (recessive or dominant)

Mendelian Disorders

• Genetic conditions caused by mutations in a single gene.
• Autosomal dominant diseases.
• Autosomal recessive diseases.
• X-linked recessive diseases.
• X-linked dominant diseases

Mitochondrial Disorders

• Mitochondrial DNA (mtDNA) is passed from mothers to their offspring.
• Mitochondrial diseases are inherited from the mother.

Prenatal Genetic Tests

• Amniocentesis and chorionic villus sampling collect fetal cells or fluid for testing.
• Karyotyping and enzyme analyses.
• Used to assess fetal health and diagnose diseases.

Genetic Testing/Screening

• The decision to pursue genetic testing and screening.
• Tests to determine carrier status for future children.
• Prenatal diagnosis

Genetic Counselors

• Provide information, support, and guidance about genetic conditions.
• Analyze inheritance and recurrence patterns.
• Identify risk families.
• Evaluate available options (treatment, care).

Prevention of Genetic Diseases

• Genetic counseling, expert consultation, to determine risk and inheritance patterns for potential genetic disorders.

Pedigree and Karyotype

• Pedigree: A family tree showing traits across multiple generations
• Karyotype: An analysis of chromosome structure and number in a sample of cells.

Methods for Studying Genetics

• PCR (Polymerase Chain Reaction): A method for amplifying specific DNA sequences.
• Southern blotting: Used to detect specific DNA sequences in a sample.
• DNA sequencing
• Single Nucleotide Polymorphism (SNP)
• Fluorescent In-situ Hybridization (FISH)
• Microarrays
• Karyotyping
• Gel electrophoresis
• Restriction Fragment Length Polymorphism (RFLP)

Diagnosis and Treatment of Genetic Diseases

• DNA, RNA, and protein-based diagnostics are used for diagnosis.
• Mutations (point mutations, insertions/deletions, frameshift mutations, chromosomal aberrations).
• Treatment focuses on managing symptoms and alleviating effects of genetic disorders.
• Therapy to modify individual behaviors (treatment) at the level of gene expression, protein folding.
• Approaches for modifying somatic genomes via transplantation techniques (stem cell, nuclear transplantation).