The Chromosomal Basis of Inheritance – Pedigrees

What is a pedigree in genetics?

A pedigree is a family tree that depicts the inter-relationships of parents and children across generations to track inheritance of traits.

List three reasons humans are poor subjects for controlled genetic research.

(1) Long generation time, (2) comparatively few offspring per mating, and (3) breeding experiments are morally unacceptable.

Which human populations are sometimes used as exceptions for pedigree studies due to genetic isolation?

Bottle-necked or isolated groups such as Ashkenazi Jews, Amish & Mennonite communities, and the Onge of the Andaman Islands.

What two types of alleles can a disease-related gene possess?

A normal (wild-type) allele and a mutant allele that causes disease symptoms.

Name the three simple Mendelian inheritance patterns commonly seen in human disease.

Autosomal dominant, autosomal recessive, and sex-linked (X-linked or Y-linked).

How can pedigrees be used to predict future offspring phenotypes?

By applying the multiplication and addition probability rules to the genotypes shown in the pedigree.

In pedigree symbols, what does a filled (shaded) square or circle represent?

An affected male (filled square) or an affected female (filled circle).

Define a genetic carrier.

A heterozygous individual who possesses one normal allele and one recessive disease allele yet displays a normal phenotype.

Why is consanguineous mating a concern for recessive disorders?

It increases the likelihood that two carriers of the same rare recessive allele will mate, elevating the risk of affected offspring.

State the two key predictions of an autosomal recessive inheritance pattern.

1) Two normal heterozygotes produce ~25 % affected offspring. 2) Two affected parents produce 100 % affected offspring.

Give two predictions of an autosomal dominant inheritance pattern.

1) An affected person usually has at least one affected parent. 2) If neither parent is affected, the case may stem from a new (de novo) mutation.

Why are lethal dominant alleles, such as those causing some skeletal dysplasias, rare in populations?

Because they often cause severe disease or death before reproduction, and thus are usually introduced only by new mutations.

What disorder is a textbook example of a rare dominant allele in humans?

Achondroplasia, a form of dwarfism.

Define an autosome.

Any chromosome that is not a sex chromosome; humans have 22 pairs of autosomes.

Describe the genetic requirement for an autosomal recessive disease to manifest.

Two abnormal (mutant) copies of a gene on an autosome must be present.

Describe the genetic requirement for an autosomal dominant disease to manifest.

Only one abnormal copy of a gene on an autosome is sufficient to cause the disease.

Why are X-linked recessive traits more common in males?

Males have only one X chromosome, so a single recessive allele on that X will manifest, whereas females need two copies.

How do Y-linked traits typically appear in pedigrees?

They affect males in every generation and are passed from father to all sons.

What is the difference between X-linked recessive and X-linked dominant inheritance in females?

Recessive: females need two mutant copies; Dominant: females need only one mutant copy to express the trait.

If an affected child is born to two unaffected parents, which inheritance mode is most likely?

Autosomal recessive (or X-linked recessive if the child is male and the mother is a carrier).

What term describes a new disease-causing allele that appears in a pedigree without being inherited from either parent?

A de novo (new) mutation.

Which probability rules are applied in pedigree analysis to calculate risk of phenotypes?

The multiplication rule (for independent events occurring together) and the addition rule (for mutually exclusive events).

What primary questions should be addressed when writing a clinical pedigree summary?

Mode of inheritance, carrier risk for relatives, and recurrence risk for future offspring.

How can the presence of carriers be inferred on a pedigree?

Carriers often appear as unaffected individuals who have affected offspring or who fall within a pattern consistent with recessive inheritance.