  The effects of inbreeding on human health depend critically on the number and
severity of recessive, deleterious mutations carried by individuals. In humans,
existing estimates of these quantities are based on comparisons between
consanguineous and non-consanguineous couples, an approach that confounds
socioeconomic and genetic effects of inbreeding. To circumvent this limitation,
we focused on a founder population with almost complete Mendelian disease
ascertainment and a known pedigree. By considering all recessive lethal
diseases reported in the pedigree and simulating allele transmissions, we
estimated that each haploid set of human autosomes carries on average 0.29 (95%
credible interval [0.10, 0.83]) autosomal, recessive alleles that lead to
complete sterility or severe disorders at birth or before reproductive age when
homozygous. Comparison to existing estimates of the deleterious effects of all
recessive alleles suggests that a substantial fraction of the burden of
autosomal, recessive variants is due to single mutations that lead to death
between birth and reproductive age. In turn, the comparison to estimates from
other eukaryotes points to a surprising constancy of the average number of
recessive lethal mutations across organisms with markedly different genome
sizes.

Populations and Evolution