A human model for multigenic inheritance: Phenotypic expression in Hirschsprung disease requires both the RET gene and a new 9q31 locus

Reduced penetrance in genetic disorders may be either dependent or independent of the genetic background of gene carriers. Hirschsprung disease (HSCR) demonstrates a complex pattern of inheritance with ≈50% of familial cases being heterozygous for mutations in the receptor tyrosine kinase RET. Even when identified, the penetrance of RET mutations is only 50–70%, gender-dependent, and varies with the extent of aganglionosis. We searched for additional susceptibility genes which, in conjunction with RET, lead to phenotypic expression by studying 12 multiplex HSCR families. Haplotype analysis and extensive mutation screening demonstrated three types of families: six families harboring severe RET mutations (group I); and the six remaining families, five of which are RET-linked families with no sequence alterations and one RET-unlinked family (group II). Although the presence of RET mutations in group I families is sufficient to explain HSCR inheritance, a genome scan reveals a new susceptibility locus on 9q31 exclusively in group II families. As such, the gene at 9q31 is a modifier of HSCR penetrance. These observations imply that identification of new susceptibility factors in a complex disease may depend on classification of families by mutational type at known susceptibility genes.

A relationship between behavior, neurotrophin expression, and new neuron survival

The high vocal center (HVC) controls song production in songbirds and sends a projection to the robust nucleus of the archistriatum (RA) of the descending vocal pathway. HVC receives new neurons in adulthood. Most of the new neurons project to RA and replace other neurons of the same kind. We show here that singing enhances mRNA and protein expression of brain-derived neurotrophic factor (BDNF) in the HVC of adult male canaries, Serinus canaria. The increased BDNF expression is proportional to the number of songs produced per unit time. Singing-induced BDNF expression in HVC occurs mainly in the RA-projecting neurons. Neuronal survival was compared among birds that did or did not sing during days 31–38 after BrdUrd injection. Survival of new HVC neurons is greater in the singing birds than in the nonsinging birds. A positive causal link between pathway use, neurotrophin expression, and new neuron survival may be common among systems that recruit new neurons in adulthood.

Fate of a redundant gamma-globin gene in the atelid clade of New World monkeys: implications concerning fetal globin gene expression.

Conclusive evidence was provided that gamma 1, the upstream of the two linked simian gamma-globin loci (5'-gamma 1-gamma 2-3'), is a pseudogene in a major group of New World monkeys. Sequence analysis of PCR-amplified genomic fragments of predicted sizes revealed that all extant genera of the platyrrhine family Atelidae [Lagothrix (woolly monkeys), Brachyteles (woolly spider monkeys), Ateles (spider monkeys), and Alouatta (howler monkeys)] share a large deletion that removed most of exon 2, all of intron 2 and exon 3, and much of the 3' flanking sequence of gamma 1. The fact that two functional gamma-globin genes were not present in early ancestors of the Atelidae (and that gamma 1 was the dispensible gene) suggests that for much or even all of their evolution, platyrrhines have had gamma 2 as the primary fetally expressed gamma-globin gene, in contrast to catarrhines (e.g., humans and chimpanzees) that have gamma 1 as the primary fetally expressed gamma-globin gene. Results from promoter sequences further suggest that all three platyrrhine families (Atelidae, Cebidae, and Pitheciidae) have gamma 2 rather than gamma 1 as their primary fetally expressed gamma-globin gene. The implications of this suggestion were explored in terms of how gene redundancy, regulatory mutations, and distance of each gamma-globin gene from the locus control region were possibly involved in the acquisition and maintenance of fetal, rather than embryonic, expression.

Taylor's sacred minstrel, or, American church music book : a new collection of psalm and hymn tunes adapted to the various metres now in use : together with anthems, sentences, chants and other pieces : for the use of choirs, congregations, singing schools, musical societies, social sacred music circles, and private devotion ... /

Mode of access: Internet.

Goethe, the lyrist : 100 poems in new translations facing the originals, with a biographical introduction by Edwin H. Zeydel ; with an appendix on musical settings to the poems.

Includes index.

Picture book of musical instruments /

Includes index.

Nelly Neil; a new musical play.

Mode of access: Internet.

A runaway girl : new musical play /

Pl. no.: 20539.

Album of intstructive pieces for the pianoforte. Arranged in progressive order, from the easiest to the medium grade of difficulty, with new phrasing, fingering and appropriate marks of expression,

Mode of access: Internet.

Catechism of musical history /

Vol. 2 has imprint: London, Augener & co.; New-York, G. Schirmer.

Musical pastime; a new collection of popular melodies, arranged as duets for the violin and piano. Consisting of the latest and best marches, galops, waltzes. polkas, round and square dances &c. Together with a choice selection of solos upon classical airs, arranged for amateurs.

Mode of access: Internet.

An inquiry into the authenticity of certain miscellaneous papers and legal instruments, published Dec. 24, MDCCXCV. and attributed to Shakspeare, Queen Elizabeth, and Henry, Earl of Southampton: illustrated by fac-similes of the genuine hand-writing of that nobleman, and of Her Majesty; a new fac-simile of the hand-writing of Shakspeare, never before exhibited; and other authentic documents: in a letter addressed to the Right Hon. James, Earl of Charlemont,

Mode of access: Internet.

Perrot's Wilhem's Musical manual : a new method for vocal classes; designed particularly for colleges, public and private schools, private classes, &c.... /

Mode of access: Internet.