After birds diverged from mammals, different ancestral autosomes evolved into sex chromosomes in each lineage. In birds, females are ZW and males ZZ, but in mammals females are XX and males XY. We sequenced the chicken W chromosome, compared its gene content with our reconstruction of the ancestral autosomes, and followed the evolutionary trajectory of ancestral W-linked genes across birds. Avian W chromosomes evolved in parallel with mammalian Y chromosomes, preserving ancestral genes through selection to maintain the dosage of broadly-expressed regulators of key cellular processes. We propose that, like the human Y chromosome, the chicken W chromosome is essential for embryonic viability of the heterogametic sex. Unlike other sequenced sex chromosomes, the chicken W did not acquire and amplify genes specifically expressed in reproductive tissues. We speculate that the pressures that drive the acquisition of reproduction related genes on sex chromosomes may be specific to the male germ line.

Amyotrophic lateral sclerosis is a degenerative disorder of motor neurons that typically develops in the 6th decade and is uniformly fatal, usually within 5 years. To identify genetic variants associated with susceptibility and phenotypes in sporadic ALS, we performed a genome-wide SNP analysis in sporadic ALS cases and controls. A total of 288,357 SNPs were screened in a set of 1,821 sporadic ALS cases and 2,258 controls from the U.S. and Europe. Survival analysis was performed using 1,014 deceased sporadic cases. Top results for susceptibility were further screened in an independent sample set of 538 ALS cases and 556 controls. SNP rs1541160 within the KIFAP3 gene (encoding a kinesin-associated protein) yielded a genomewide significant result (P ‫؍‬ 1.84 ؋ 10 ؊8 ) that withstood Bonferroni correction for association with survival. Homozygosity for the favorable allele (CC) conferred a 14.0 months survival advantage. Sequence, genotypic and functional analyses revealed that there is linkage disequilibrium between rs1541160 and SNP rs522444 within the KIFAP3 promoter and that the favorable alleles of rs1541160 and rs522444 correlate with reduced KIFAP3 expression. No SNPs were associated with risk of sporadic ALS, site of onset, or age of onset. We have identified a variant within the KIFAP3 gene that is associated with decreased KIFAP3 expression and increased survival in sporadic ALS. These findings support the view that genetic factors modify phenotypes in this disease and that cellular motor proteins are determinants of motor neuron viability.genome-wide association study ͉ single nucleotide polymorphism A myotrophic lateral sclerosis (ALS) is an age-dependent, degenerative disorder of motor neurons (1) that typically develops in the 6th decade and is uniformly fatal, usually within 5 years (2). Approximately 10% of ALS cases are dominantly inherited (3); 20% of these are caused by mutations in the gene encoding copper/zinc superoxide dismutase 1 (SOD1) (4); mutations in the TARDBP gene (5, 6) account for Ϸ5% of cases. Rare familial cases arise from mutations in genes encoding the vesicle-associated membrane associated protein B (7), alsin (a RAB5-guanine nucleotide exchange factor) (8, 9), senataxin (10) or dynactin (11). Recently, we reported that Ϸ5% of familial ALS cases are due to mutations in the FUS/TLS gene (12, 13) whose product binds DNA and RNA, as does TARDBP. The cause of sporadic ALS is thought to be multifactorial, with environmental, infectious and genetic etiologies. Reported associations with variants in diverse genes (14-25) have proven difficult to replicate. Advances in the technology for large-scale genotyping of single nucleotide polymorphisms (SNPs) have facilitated unbiased, genome-wide association studies. Examples include the identification of IL2RA and IL7RA variants as risk factors for multiple sclerosis (26-28) and the recent reports of 6 new gene regions associated with type 2 diabetes (29)(30)(31)(32)(33)(34)(35). To test the hypothesis that commonly occurring genetic