Pedigree Analysis: Six Modes of Inheritance

The inheritance of many monogenic (single-gene) traits can be determined
    by the analysis of family trees (pedigrees) (IG1 15.22)
        Pedigrees show relationships among individuals
        Ex.: Queen Victoria's pedigree shows genetic inheritance of Hemophilia A

Six basic Modes of Inheritance
      Distinguish autosomal vs sex-linked conditions
           sex (X) - linked conditions affect predominantly males
           autosomal conditions affect male and females equally

    1. Autosomal recessive
           ex.: Oculocutaneous Albinism (OMIM203100)
                     Batten Disease (OMIM204200): high frequency in Newfoundland
                     PTC tasting (OMIM1720) (Homework)

             Clues: Condition is
usually rare (allele frequency is low)
                         Allele is usually present in heterozygous genotypes
                         Condition often occurs in matings of related individuals
                                consanguineous marriage - at least one ancestor in common
"inbreeding" - consanguineous marriages occur more frequently than expected
                         Conditions often "skips generations"

    2. Autosomal dominant
              ex.: Achondroplasia (OMIM100800)
                      Huntington Disease (OMIM143100)
                     Arrthymogenic Right Ventricular Dysplasia, Type 5 (ARVD5) (OMIM604400)
                            "Newfoundland's sudden-death riddle resolved" (Globe & Mail 29 Feb 2008)

                     Hereditary nonpolyposis colorectal cancer
                      ACHOO syndrome (OMIM100820 ) - photic sneezing
                      Fatal Familial Insomnia (OMIM600072) - a prion disease

              Clues: Allele is usually present in heterozygous genotype
                          Condition must appear in every generation

    3. X-linked recessive
              ex.: Hemophilia A (OMIM 306700)
                      Testicular Feminization Syndrome (OMIM300068)
                      Red-Green Colour Deficiency (OMIM306800)

              Clues: Condition occurs predominantly in males
                          Affected males usually do not have affected offspring
              Criss-Cross inheritance: affected males & females alternate among generations

  4. X-linked dominant
Hypophosphatemia (OMIM 307800) (XLH)

               Clues: Affected males always pass the condition to daughters
                           Affected females are usually heterozygous

    5. Y-linked
             ex.: Zinc-Finger Protein, Y-linked (ZFY) (OMIM490000)
                    Sex-determining Region Y (SRY) (OMIM480000)
                    Hairy Ears (OMIM425500) probably not Y-linked: a sex-limited trait

                   Clues: Condition occurs in all male descendants, and only males
                                Phenotypes are typical of males

     6. mtDNA-linked
             ex.:  The "Daughters of Eve" in Newfoundland
                      Matrilineal descendants of Queen Victoria           
             mitochondrial DNA
(mtDNA) is a cytoplasmic (non-nuclear) genome

                   Clues: occurs in all descendants of an affected female
                                Affected males do not transmit the condition

[Not covered in 2012; not on final exam]

Calculation of Risk in pedigree analysis involves simple probability theory
       The probability of two independent events occurring together ("A and B")
                is the product of the separate probabilities
       The probability of two alternative events occurring together ("A or B")
                is the sum of their separate probabilities
       The a priori probability of events may be modified by a posteriori knowledge
                calculation of the probability of single events is often influenced a posteriori

Homework: In the following pedigrees, which modes of inheritance can be ruled out?
                           What individual(s) allow you to do so?
                      Which are possible? Which is most likely? Explain.
                                                                Write out the genotypes of each of the individuals.

     Pedigree #1
     Pedigree #2
     Pedigree #3

MGA2 Chapter 5: Problems 2*, 10, 11, 13, 19, 20
iGen2 Chapter 12: Problems 42, 43, 44, 45, 46, 47

All text material ©2012 by Steven M. Carr