bias is a systematic distortion in measuring the true
frequency of a phenomenon due to the way in which the data are
collected. In genetics, ascertainment bias is an important factor
in the use of family pedigree data to establish modes of
inheritance of the genetic condition Alkaptonuria,
characterized by excretion of high amounts of "alkapton" (Homogentisic Acid) in the
urine. This is a autosomal
recessive trait, such that almost all persons born
with the condition (aa) will be the offspring of two
unaffected heterozygous carrier (Aa) parents. Thus,
according to ordinary Mendelian principles, among a large group of
Aa x Aa crosses, 1/4
of offspring are expected to show the condition. Recognition of
such a ratio would be an important clue to the pattern of
Alkaptonuria was the first human medical trait to be identified as genetic In the first inquiry into the genetics of this condition, Garrod (1902) reported the following data:
Given the birth of
offspring with alkaptonuria (aa) to "normal" parents, the parents
must all be carriers (Aa). Then, among a total of 48
offspring of such parents, the expected
ratio should be 1:3 or 12 alkaptonuric : 36 normal
members. The observed ratio
is 19 : 29, that is,
significantly more alkaptonurics are present in the sample than
expected from the genetic model. Why is this?The answer is the way
in which Garrod collected his data.
One source of ascertainment bias is that
Garrod was a physician, and saw people who consulted him medially.
His data tables includes only families in which at
least one child has alkaptonuria. Note for example that for
3/4 of Aa parents with
one child, that child will be unaffected, and the family has no
reason to consult him. Thus a large number of families of Aa parents and 1, 2, 3, or
more unaffected children
are excluded from his counts.
A second source is the greater likelihood that families with a higher number of alkaptonuric children will consult Garrod: they are more likely to seek advice than families in which the condition is confined to a single child. In the table, 6 of 9 families reported have more than one affected child, and in all of these (except family #7) the observed ratio of affected children exceeds 1:3. Indeed, without family #7, the observed proportion would be 18:20, effectively 1:1, which might imply autosomal dominant inheritance in which Aa x aa => 50% Aa: 50% aa. This will again systematically bias the data towards a higher proportion of affected children.
A classroom demonstration of
ascertainment bias is a survey for the primary sex ratio in humans.
[Homework: Test the deviation between Garrod's observed and expected results by the Chi-Square test].