LESSON 2

• OMIM describes about 8,000 single-gene diseases and traits, corresponding to about 23,000 genes
• Mutations in single genes are referred to as monogenic
• Characteristics of single-gene diseases:

  • Inherited illnesses caused by mutations in single genes
  • Test can sometimes predict the risk of developing symptoms
  • Single-gene diseases may be much more common in some populations than others
  • Can be fixable by compensating for the abnormal instructions
• Modes of inheritance:

  • Autosomal dominant: affects both sexes and appears every generation
  • Autosomal recessive: disease affects both sexes and can skip generations through carriers
• Gregor Mendel:

  • Father of genetics
  • Single-gene traits and diseases are also called "Mendelian" in honor of Gregor Mendel
  • Derived the two laws of inheritance that determine how traits are transmitted from one generation to the next
  • Started with Pea plants
• Mendel's experiments timeline:

  • 1857-1863: Mendel crossed and cataloged traits in 24,034 plants, deducing consistent ratios of traits in the offspring
  • 1877: Mendel published his findings
  • 1901: Credited with deducing the two basic laws of inheritance
  • Early 1900s: Mendel's ratios seen in several species, coinciding with the discovery of chromosomes
  • 1909: William Bateson renamed Mendel's elementen genes
  • 20th Century: Researchers discovered the molecular basis of certain traits Mendel studied
• Generations of Mendel's genetic crosses:

  • Parental generation: First generation
  • F1 first filial generation: Second generation
  • F2 second filial generation: Third generation
• Mendel's first experiments:

  • Followed single traits with two expressions, such as "short" and "tall"
  • Crossed plants with different traits to produce hybrids
  • Monohybrid cross follows one trait and the self-crossed plants are hybrids
• Law of segregation:

  • Elementen separate in the gametes
• Terms and tools to follow segregating genes:

  • Homozygous: individual with two identical alleles
  • Heterozygous: individual with two different alleles
  • Homozygous recessive: both alleles are recessive
  • Homozygous dominant: two dominant alleles
  • Heterozygote: one dominant and one recessive allele
  • Compound heterozygote: individual with two different recessive alleles for the same gene
• Phenotype and genotype:

  • Genotype describes the organism's allele
  • Phenotype describes the outward expression of an allele combination
  • Wild type phenotype is the most common expression of a particular allele combination
  • Mutant phenotype is a variant of a gene's expression that arises from a mutation
• Punnett square:

  • Represents how genes in gametes join if they are on different chromosomes
• Modes of inheritance:

  • Autosomal dominant inheritance: a trait can appear in either sex and does not skip generations
  • Autosomal recessive inheritance: a trait can appear in either sex, affected individuals have a homozygous recessive genotype
• Consanguinity:

  • Occurs in marriage between relatives
  • Alleles inherited from shared ancestors are said to be "identical by descent"
• Solving a problem in following a single gene:

  1. List all possible genotypes and phenotypes for the trait

  2. Determine the genotypes of the individuals in the first generation

  3. Deduce genotypes and derive possible alleles in gametes

  4. Unite gametes in all combinations to reveal all possible genotypes and calculate ratios for the F1 generation

  5. Use genotypes of specified F1 individuals to predict the F2 generation
• Mendel's second law:

  • Law of independent assortment states that for two genes on different chromosomes, the inheritance of one gene does not influence the chance of inheriting the other gene
• Solving a problem in following multiple genes:

  • Punnett square for three genes has 64 boxes; for four genes, 256 boxes
  • Use mathematical laws of probability to predict genotypes and phenotypes in multigene crosses
• Probability that are the basis of Punnett squares
• Product rule:

  • An application of probability theory
  • Can predict the chance that parents with known genotypes can produce offspring of a particular genotype
• Pedigree analysis:

  • Pedigrees are used to display family relationships and depict which relatives have specific phenotypes and, sometimes, genotypes
  • A pedigree in genetics differs from a family tree in genealogy and from a genogram in social work, as it indicates inherited diseases or traits as well as relationships and ancestry
• Modes of inheritance:

  • Autosomal dominant:
  • Affects both sexes and appears every generation
  • Example: Huntington's disease
  • Sex chromosomes (XX, XY)
  • 22 autosomes
  • 1 pair of autosomes can bring sex chromosomes
  • Autosomal recessive:
  • Affects both sexes and can skip generations through carriers who don't have the symptoms
  • Example: Cystic fibrosis
• Mendel's experiments:

  • Traits are passed on from generation to generation
  • Mendel conducted experiments from 1857 to 1863 on traits in 24,034 plants through several generations
  • He focused on the length (short x short) resulting in the short offspring
  • True breeding:
  • Always produces the same phenotype as the parent
  • Hybrid:
  • Offspring that inherit a different gene variant (allele) from each parent
• Monohybrid cross:

  • Mendel conducted up to 70 hybrid self-crosses for each of the seven traits
  • Phenotype: manifest outside (100% or 4 or 3 Purple: 1 White)
  • Genotypes: represented by alleles (1PP:2Pp:1pp)
• Law of segregation:

  • Reflects the actions of chromosomes and the genes they carry during meiosis
  • Homozygous: two identical alleles for a gene (TT, tt)
  • Heterozygous: two different alleles, "non-true breeding" or "hybrid"
  • Examples: RR (homo dominant), Rr (Hetero dominant), rr (Homo recessive)
• Solving genetic problems:

  • List all genotypes and phenotypes for the trait
  • Determine the genotypes of the parents
  • Drive possible alleles in gametes
  • Unite gametes in all combinations to reveal all possible genotypes
  • Report of successive generation
• Law of independent assortment:

  • For two genes on different chromosomes, the inheritance of one does not influence the chance of inheriting the other gene
  • Two genes that are far apart on the same chromosome appear to independently assort
• Dihybrid cross:

  • Round (RR) yellow (YY) x Wrinkled (rr) Green (yy)
  • Probability:
  • The likelihood that an event will occur
  • Product rule: Probability of simultaneous independent events equals the product of their individual probabilities
• Pedigree analysis:

  • Flow chart of the family
  • Pedigrees are symbolic representations of family relationships and the transmission of inherited traits
• Autosomal recessive trait:

  • Albinism = deficiency in melanin production
  • Parents are inferred to be heterozygotes
• Polydactyl = excess toes and fingers