👨‍👩‍👦‍👦General Genetics Unit 4 – Chromosomal Theory of Inheritance

Key Concepts and Terminology

• Alleles refer to alternative forms of a gene that occupy the same locus on homologous chromosomes and influence the same trait
• Genotype describes an individual's genetic makeup, while phenotype refers to the observable characteristics resulting from the genotype and environmental factors
• Homologous chromosomes are pairs of chromosomes, one inherited from each parent, that carry the same genes but may have different alleles
• Haploid cells contain a single set of chromosomes (n), while diploid cells have two sets (2n)
• Meiosis is a type of cell division that produces haploid gametes (eggs and sperm) from diploid cells
  • Meiosis I separates homologous chromosomes, while meiosis II separates sister chromatids
• Mitosis is a type of cell division that produces two genetically identical daughter cells from a single parent cell
• Recombination is the exchange of genetic material between homologous chromosomes during meiosis, resulting in new combinations of alleles

Historical Background

• Gregor Mendel, an Austrian monk, conducted experiments on pea plants in the mid-19th century, laying the foundation for modern genetics
  • Mendel's work was largely ignored until the early 20th century when it was rediscovered and validated
• Walter Sutton and Theodor Boveri independently proposed the chromosomal theory of inheritance in the early 1900s
  • They observed the behavior of chromosomes during meiosis and recognized their role in heredity
• Thomas Hunt Morgan and his colleagues conducted experiments on fruit flies (Drosophila melanogaster) that provided strong evidence for the chromosomal theory of inheritance
  • Morgan's work led to the discovery of genetic linkage and the mapping of genes on chromosomes
• The discovery of DNA as the genetic material by Oswald Avery, Colin MacLeod, and Maclyn McCarty in 1944 further supported the chromosomal theory of inheritance
• James Watson and Francis Crick's discovery of the double helix structure of DNA in 1953 revolutionized our understanding of the molecular basis of heredity

Structure and Function of Chromosomes

• Chromosomes are thread-like structures found in the nucleus of eukaryotic cells that carry genetic information in the form of DNA
• Each chromosome consists of a single, long DNA molecule tightly coiled around proteins called histones
  • The DNA-protein complex is called chromatin, which condenses to form chromosomes during cell division
• Chromosomes have a centromere, a constricted region that plays a crucial role in the separation of chromosomes during cell division
  • The centromere divides the chromosome into two arms: the short arm (p-arm) and the long arm (q-arm)
• Telomeres are repetitive DNA sequences found at the ends of chromosomes that protect them from degradation and fusion with other chromosomes
• Genes are specific segments of DNA located at specific positions (loci) on chromosomes that encode instructions for the production of proteins or functional RNA molecules
• The number and structure of chromosomes vary among species
  • Humans have 23 pairs of chromosomes (22 pairs of autosomes and one pair of sex chromosomes), for a total of 46 chromosomes in diploid cells

Mendel's Laws and Chromosomal Theory

• Mendel's law of segregation states that alleles for a trait separate during gamete formation, and each gamete receives only one allele for each gene
  • This law is explained by the separation of homologous chromosomes during meiosis I
• Mendel's law of independent assortment states that alleles for different traits are inherited independently of one another
  • This law is explained by the random alignment of homologous chromosome pairs during metaphase I of meiosis
• The chromosomal theory of inheritance proposes that genes are located on chromosomes and that the behavior of chromosomes during meiosis accounts for Mendel's laws
• Genes located on the same chromosome are said to be linked and do not follow the law of independent assortment
  • Linked genes are more likely to be inherited together, while genes on different chromosomes assort independently
• The frequency of recombination between two genes on the same chromosome depends on the distance between them
  • Genes that are farther apart have a higher probability of recombination due to crossing over during meiosis

Genetic Linkage and Crossing Over

• Genetic linkage refers to the tendency of genes located on the same chromosome to be inherited together
• Linked genes do not follow Mendel's law of independent assortment and are more likely to be passed on to offspring in their original combination
• Crossing over is the exchange of genetic material between homologous chromosomes during prophase I of meiosis
  • Crossing over results in the formation of new combinations of alleles on the chromosomes
• The frequency of crossing over between two genes depends on the distance between them on the chromosome
  • Genes that are farther apart have a higher probability of crossing over
• Genetic maps, also called linkage maps, are constructed based on the frequency of recombination between genes
  • The distance between genes on a genetic map is measured in centimorgans (cM), with 1 cM representing a 1% chance of recombination
• Recombination frequencies can be used to determine the order and relative distances of genes on a chromosome
• Genetic linkage and crossing over explain the observation of linked inheritance and the formation of new allele combinations

Sex Chromosomes and Sex-Linked Inheritance

• Sex chromosomes are a pair of chromosomes that determine an individual's sex
  • In humans, females have two X chromosomes (XX), while males have one X and one Y chromosome (XY)
• Autosomes are chromosomes that are not directly involved in determining sex and are present in two copies in both males and females
• Sex-linked genes are genes located on the sex chromosomes, primarily the X chromosome
  • Few genes are located on the Y chromosome, which is much smaller than the X chromosome
• X-linked inheritance refers to the inheritance pattern of genes located on the X chromosome
  • Males are hemizygous for X-linked genes, meaning they have only one copy of the gene
  • Females can be homozygous or heterozygous for X-linked genes
• X-linked recessive disorders (Hemophilia, Duchenne muscular dystrophy) are more common in males because they only need one copy of the mutated allele to express the disorder
• X-linked dominant disorders (Rett syndrome, Fragile X syndrome) affect both males and females, but males are often more severely affected
• Y-linked inheritance refers to the inheritance pattern of genes located on the Y chromosome
  • Y-linked genes are passed from father to son and are not present in females

Chromosomal Abnormalities and Disorders

• Chromosomal abnormalities are changes in the number or structure of chromosomes that can lead to genetic disorders
• Numerical abnormalities involve changes in the number of chromosomes
  • Aneuploidy is the presence of an abnormal number of chromosomes, such as trisomy (extra chromosome) or monosomy (missing chromosome)
  • Polyploidy is the presence of more than two complete sets of chromosomes, such as triploidy (3n) or tetraploidy (4n)
• Structural abnormalities involve changes in the structure of chromosomes
  • Deletions occur when a portion of a chromosome is lost
  • Duplications occur when a portion of a chromosome is duplicated
  • Inversions occur when a segment of a chromosome breaks off, reverses orientation, and reattaches
  • Translocations occur when a segment of one chromosome attaches to another chromosome
• Down syndrome (trisomy 21) is caused by an extra copy of chromosome 21 and is characterized by intellectual disability and distinctive facial features
• Turner syndrome (45,X) is caused by the absence of one X chromosome in females and is characterized by short stature and infertility
• Klinefelter syndrome (47,XXY) is caused by an extra X chromosome in males and is characterized by tall stature, infertility, and learning difficulties
• Cri-du-chat syndrome (5p deletion) is caused by a deletion on the short arm of chromosome 5 and is characterized by intellectual disability, microcephaly, and a distinctive cat-like cry in infancy

Modern Applications and Research

• Karyotyping is a technique used to visualize and analyze an individual's chromosomes
  • Karyotypes can be used to diagnose chromosomal abnormalities and genetic disorders
• Fluorescence in situ hybridization (FISH) is a technique that uses fluorescent probes to detect specific DNA sequences on chromosomes
  • FISH can be used to identify chromosomal abnormalities, gene deletions, and gene amplifications
• Comparative genomic hybridization (CGH) is a technique that compares the DNA content of two samples to identify differences in copy number
  • CGH can be used to detect chromosomal imbalances and identify regions of DNA gain or loss
• Next-generation sequencing (NGS) technologies allow for the rapid sequencing of entire genomes or targeted regions of interest
  • NGS can be used to identify genetic variations, mutations, and structural variations associated with genetic disorders
• Genome-wide association studies (GWAS) are used to identify genetic variations associated with complex traits and diseases
  • GWAS involve comparing the genomes of individuals with and without a particular trait or disease to identify associated genetic markers
• Gene therapy is a promising approach for treating genetic disorders by introducing functional copies of genes into cells to replace or compensate for defective genes
  • Gene therapy has been successfully used to treat some rare genetic disorders, such as severe combined immunodeficiency (SCID)
• CRISPR-Cas9 is a powerful gene-editing tool that allows for precise modification of DNA sequences
  • CRISPR-Cas9 has the potential to be used for the treatment of genetic disorders, but ethical concerns surrounding its use need to be addressed