Pedigree Analysis: Six Modes of Inheritance

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

Six basic Modes of Inheritance
    Dominant vs Recessive transmission     
    autosomal vs sex-linked traits
           X - linked traits affect predominantly males
           Y - linked traits affect only males
           autosomal traits affect males & females equally
    mtDNA - linked affect both, passed only through females   

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Consult Online Mendelian Inheritance in Man (OMIM) for examples of 'genetic' traits
                N.B.: Many classical human genetic conditions are not determined by a single gene locus:
                       e.g., eye colour

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

             Clues: trait is usually rare (allele frequency is low)
                         Allele is usually present in heterozygous genotypes
                         trait often occurs in matings of related individuals
                                consanguineous marriage - at least one ancestor in common, versus
                                "inbreeding" - consanguineous marriages occur more frequently than expected
                          trait often "skips generations"
              Ascertainment Bias in use of pedigree data

    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 (HNPCC)
                      ACHOO syndrome (OMIM100820 ) - photic sneezing
                      Fatal Familial Insomnia (OMIM600072) - a prion disease
                     
              Clues: Allele is usually present in heterozygous genotype
                          trait must appear in every generation

                 Marker-assisted genetic diagnosis (IG1 15.22)

    3. X-linked recessive
              ex.: Hemophilia A (OMIM 306700)
                     Testicular Feminization Syndrome (OMIM300068)
                     Red-Green Colour Deficiency (OMIM306800)
 
              Clues: trait occurs predominantly in males
                          Affected males usually do not have affected offspring
                         "Criss-Cross inheritance": affected males & females alternate between generations

               X-linked Co-Dominant: the genetics of tortoiseshell & calico cats

    4. X-linked dominant
              ex.: Hypophosphatemia (OMIM 307800)
 
               Clues: Affected males always pass the trait to daughters
                           Affected females are usually heterozygous

    5. Y-linked