Lecture 17: Pedigrees Flashcards
Mendelian inheritance in humans
Most traits in humans are due to the interaction of multiple genes and do not show a simple Mendelian pattern of inheritance
•A few traits represent single-genes: e.g. sickle-cell anemia, cystic fibrosis, Tay-Sachs disease, Huntington’s disease
•Because we can not do breeding experiments on humans, we must use pedigrees to study inheritance
Pedigrees
are an orderly diagram of a families relevant genetic features extending through multiple generations
•Typically small number of offspring
•Mendelian ratios rarely observed
Pedigrees help us infer if a trait is from a single gene and if the trait is dominant or recessive
•Allow inferences concerning genotypes and predictions concerning phenotypes of offspring (genetic counseling)
Autosomal dominant disorders
Abnormal disorder gene is dominant
•Normal, wild type allele is recessive
- Inherited in a simple Mendelian dominant manner:
- The phenotype appears in every generation
- Each individual in the pedigree that is affected has affected parents
- Affected fathers and mothers transmit the phenotype to both sons and daughters
- An heterozygote parent typically transmits the trait to ½ of their progeny
e.g. Pseudo-achondroplasia (dwarfism), Huntington disease, polydactyly, brachydactyly, piebald spotting
Autosomal recessive disorders
Abnormal, disorder-causing gene is recessive
•Normal, wild type allele is dominant
Inherited in a simple Mendelian recessive manner:
•Trait appears in individuals whose parents are normal
•The trait may skip generations
•The affected progeny include both males and females
•Two normal heterozygote parents typically produce a 3:1 ratio of normal to recessive progeny
E.g. PKU, albinism, sickle cell anemia
Autosomal recessive traits/disorders
- Only homozygous recessive individuals exhibit the affected phenotype
•Males and females are equally affected and may transmit the trait
•May skip generations
How do sex chromosomes relate to the sex of the organism?
44A XX is female
•Homogametic (only X gametes/eggs)
- 44A XY is male
- Heterogametic (X and Y gametes/sperm)
- Segregate equally into gametes at meiosis
•Offspring - ½ XX (female):½ XY (male)
Sex Linkage
Look in text
X-linked inheritance
Females: 3 possible X-linked genotypes
XAXA XAXa XaXa
•Males: 2 possible X-linked genotypes
XAY XaY
Characteristics of inheritance: sex-linked
X-linked recessive
•The results of a reciprocal cross are not the same
•Males exhibit the trait more than females
•Female heterozygotes (unaffected carriers) for the trait pass it on to ½ of their sons
•Daughters of heterozygote mothers (unaffected carriers) and normal fathers have a 1:1 ratio of normal (homozygotes) to carriers (heterozygotes)
X-linked dominant
•The results of the reciprocal crosses are not the same
•Females exhibit the trait more than males
•Female heterozygotes for the trait (affected) pass it on to ½ of their daughters and ½ of their sons
•Sons (affected) pass on the trait to all of their daughters but none of their sons.
X-linked recessive disorders
Abnormal disorder-causing allele is recessive and is located on the X-chromosome
•Normal, wild type allele is dominant
•More males than females show the disorder
Offspring of an affected male:
•Sons - none are affected, nor will they transmit the condition to their offspring
•Daughters – none are affected, but all are carriers; half of their sons are affected (and half of their daughters are carriers)
•e.g. red-green colourblindness, hemophilia, Duchenne muscular dystrophy, testicular feminization syndrome
X-linked dominant disorders
Abnormal disorder-causing allele is dominant and is located on the X-chromosome
•Normal, wild type allele is recessive
•Affected males transmit the condition to all their daughters but none of their sons
•Affected heterozygous females transmit the condition to half their sons and daughters
•e.g. hypophosphatemia (Vitamin D-resistant rickets)
