Wilhelm Weinberg’s Early Contribution to Segregation Analysis

Abstract

Wilhelm Weinberg (1862-1937) is a largely forgotten pioneer of human and medical genetics. His name is linked with that of the English mathematician G. H. Hardy in the Hardy-Weinberg law, pervasive in textbooks on population genetics since it expresses stability over generations of zygote frequencies AA, Aa, aa under random mating. One of Weinberg's signal contributions, in an article whose centenary we celebrate, was to verify that Mendel's segregation law still held in the setting of human heredity, contrary to the then-prevailing view of William Bateson (1861Bateson ( -1926, the leading Mendelian geneticist of the time. Specifically, Weinberg verified that the proportion of recessive offspring genotypes aa in human parental crossings Aa · Aa (that is, the segregation ratio for such a setting) was indeed p ¼ 1 4 . We focus in a nontechnical way on his procedure, called the simple sib method, and on the heated controversy with Felix Bernstein in the 1920s and 1930s over work stimulated by Weinberg's article.

Determinants of mammalian nucleolar architecture

“…Ribosome assembly begins in the nucleolus, moves to the nucleoplasm, and concludes in the cytoplasm. While this complex process has traditionally been studied in the yeast Saccharomyces cerevisiae (reviewed in Henras et al 2008; Woolford Jr. and Baserga 2013), efforts have recently been made to understand the process in mammalian cells (O'Donohue et al 2010; Sloan et al 2013; Tafforeau et al 2013; Wang et al 2014; Wild et al 2010). In addition to ribosome assembly, the nucleolus may play several other roles.…”

A Reality Check on Hardy–Weinberg

“…Weinberg was a prominent member of the German ‘school’ of genetics in the first third of the 20th century, which also included Fritz Lenz and the mathematician Felix Bernstein (Baur et al, 1931; Bernstein 1925). Kallmann (1938) and Früh (1996) give accounts of Weinberg's lifework (see also Stark & Seneta, 2013). Crow (1999) contains a synthesis, and also writes on the Hardy–Weinberg setting.…”

Renal genetics in transition

“…18,19 The defect can be in one autosomal allele (autosomal dominant disease), two autosomal alleles (autosomal recessive disease), or it can be in a gene on the X or Y chromosome (sex linked disease). 18,19 12 Chapter 1 Figure 1.1 | The process of gene panel testing for renal disease: gene panel design with the use of next-generation sequencing techniques, variant calling, and interpretation, as well as the infl uence of phenotyping and segregation analysis in variant interpretation and translating the result back to the individual patient.Defi nite calling of pathogenicity is impossible however, if a variant is detected in a gene that has not previously been associated with the patient's phenotype. 19,39 In those cases, in vitro or in vivo functional studies can be performed to determine the causal relationship between mutations in a certain gene and a particular phenotype.…”

“…18,19 12 Chapter 1 Figure 1.1 | The process of gene panel testing for renal disease: gene panel design with the use of next-generation sequencing techniques, variant calling, and interpretation, as well as the infl uence of phenotyping and segregation analysis in variant interpretation and translating the result back to the individual patient.Defi nite calling of pathogenicity is impossible however, if a variant is detected in a gene that has not previously been associated with the patient's phenotype. 19,39 In those cases, in vitro or in vivo functional studies can be performed to determine the causal relationship between mutations in a certain gene and a particular phenotype. [40][41][42][43][44][45][46][47] For example, by showing that cells or a model organism in which the gene is knocked out show a phenotype similar to the patient.…”

“…Depending on the disease, a MGKD patient has up to 50%chance of passing the disease on to their off spring. 18,19 Depending on disease severity, patient preference and local availability, MGKD couples have many options regarding family planning. These include testing whether a fetus carries the same MGKD with prenatal diagnostics (PND).…”