Introduction to Pedigrees.

1.- Mendelian modes of inheritance. Shortly after the re-discovery of Mendel's work, Sir Archibald Garrod published an article in Lancet 13th December 1902 showing evidence of recessive mendelian inheritance of the human disease Alkaptonuria (black urine), and suggesting that Cystinuria may follow the same pattern. In 1905, Farabee reported the first human autosomal dominant trait, Brachydactily, (shortened fingers and toes). The facts about the inheritance of Haemophilia and red-green colour blindness were interpreted as following a sex-limited mendelian inheritance by W. Bateson (1909). Victor McKusick's OMIM (On-line Mendelian Inheritance in Man) is a public database containing up to date information on over 10,000 entries, which will be often referred to throughout this course. Here we will review how these modes of inheritance are recognised in human families.

	Standard autosomal dominant (AD) disease; One parent is affected. Both sexes affected in equal proportions. Ratio affected:non-affected = 1:1
Before doing any laboratory tests, or before having had any children, the prior probability that the child of a person affected with an autosomal dominant gene has the same gene is 1/2.
	Standard autosomal recessive disease; Neither parent affected. Both sexes can be affected in equal proportions. Ratio affected:non-affected = 1:4
Before showing any symptoms, or doing any laboratory tests, or before having had any children, the prior probability that the child of a couple carrying an autosomal recessive gene is affected is 1/4, and the probability that he/she is a carrier is 1/2.
	Standard sex-linked disease. Only males affected. 1/2 of females are unaffected 'carriers'. 1/2 of the carriers' sons are affected. A woman whose brother is affected and who has an affected son is an 'obligate' carrier. II.1
The prior probability that the daughter of an obligate carrier is a carrier is 1/2.

Prior probabilities may need to be modified in view of lab results or on finding additional family history. For instance, in the sex-linked pedigree above, the a priori risk of II2 beign a carrier, (i.e., before she had any children) was 1/2. But having had three unaffected sons makes her less likely to be a carrier. The prior risks are modified unsing Baye's theorem.