Natural selection maximizes Fisher information

In biology, information flows from the environment to the genome by the process of natural selection. However, it has not been clear precisely what sort of information metric properly describes natural selection. Here, I show that Fisher information arises as the intrinsic metric of natural selection and evolutionary dynamics. Maximizing the amount of Fisher information about the environment captured by the population leads to Fisher's fundamental theorem of natural selection, the most profound statement about how natural selection influences evolutionary dynamics. I also show a relation between Fisher information and Shannon information (entropy) that may help to unify the correspondence between information and dynamics. Finally, I discuss possible connections between the fundamental role of Fisher information in statistics, biology and other fields of science.     

What was Fisher's fundamental theorem of natural selection and what was it for?

Fisher's 'fundamental theorem of natural selection' is notoriously abstract, and, no less notoriously, many take it to be false. In this paper, I explicate the theorem, examine the role that it played in Fisher's general project for biology, and analyze why it was so very fundamental for Fisher. I defend and Lessard (1997) in the view that the theorem is in fact a true theorem if, as Fisher claimed, 'the terms employed' are 'used strictly as defined' (1930, p. 38). Finally, I explain the role that projects such as Fisher's play in the progress of scientific inquiry.     

Perspective: Here's to Fisher,additive genetic variance,and the fundamental theorem of natural selection

Fisher's fundamental theorem of natural selection, that the rate of change of fitness is given by the additive genetic variance of fitness, has generated much discussion since its appearance in 1930. Fisher tried to capture in the formula the change in population fitness attributable to changes of allele frequencies, when all else is not included. Lessard's formulation comes closest to Fisher's intention, as well as this can be judged. Additional terms can be added to account for other changes. The "theorem" as stated by Fisher is not exact, and therefore not a theorem, but it does encapsulate a great deal of evolutionary meaning in a simple statement. I also discuss the effectiveness of reproductive-value weighting and the theorem in integrated form. Finally, an optimum principle, analogous to least action and Hamilton's principle in physics, is discussed.     

Fisher’s fundamental theorem of inclusive fitness and the change in fitness due to natural selection when conspecifics interact

Competition and cooperation is fundamental to evolution by natural selection, both in animals and plants. Here, I investigate the consequences of such interactions for response in fitness due to natural selection. I provide quantitative genetic expressions for heritable variance and response in fitness due to natural selection when conspecifics interact. Results show that interactions among conspecifics generate extra heritable variance in fitness, and that interacting with kin is the key to evolutionary success because it translates the extra heritable variance into response in fitness. This work also unifies Fisher’s fundamental theorem of natural selection (FTNS) and Hamilton’s inclusive fitness (IF). The FTNS implies that natural selection maximizes fitness, whereas Hamilton proposed maximization of IF. This work shows that the FTNS describes the increase in IF, rather than direct fitness, at a rate equal to the additive genetic variance in fitness. Thus, Hamilton’s IF and Fisher’s FTNS both describe the maximization of IF.     

Second report on the inheritance of colour in pigeons,together with an account of some experiments on the crossing of certain races of Doves,with special reference to sex-limited inheritance

Journal of Genetics - The experiments have been subsidised by the Government Grant Committee of the Royal Society. I am indebted to Mr Bonhote for the Irish Rock Doves used in these crosses, and...     

Zoosporic Phycomycetes from Hispaniola

Summary Forty-five taxa of zoosporic Phycomycetes are recorded from Hispaniola (Dominican Republic) based on 34 samples collected by the senior author in December–January 1969/70. New species are Entophlyctis obscura, Phlyctochytrium parasitans, P. mucosum, Blyttiomyces harderi, Rhizophlyctis tropicalis, Chytriomyces multioperculatus.Supported in part by N. S. F. Grant GB 3333. It was originally hoped to collect species of Physoderma on Hispaniola but none was found during the few days available for exploration.I am indebted to Prof. I. Bonnelly de Calventi, Director, Inst. de Biologia marina, Univ. Autonoma de Santo Domingo, for many courtesies.     

Biophysical Reviews’ “Meet the Councilor”—a profile of Anastasia A. Anashkina

As one of the twelve Councilors of the International Union of Pure and Applied Biophysics elected in summer 2021, I have been asked to provide this short biographical sketch for the journal readers. I am a new member of the IUPAB Council. I hold a specialist degree in Applied Physics and Mathematics from the Moscow Institute of Physics and Technology and PhD in Biophysics from Moscow State University. I have spent my entire professional career at Engelhardt Institute of Molecular Biology of the Russian Academy of Sciences in Moscow, where I am currently a senior researcher. I am Associate Professor at the Digital Health Institute of the I.M. Sechenov First Moscow State Medical University since 2018, and have trained undergraduate students in structural biology, biophysics, and bioinformatics. In addition, I serve as the Guest Editor of special journal issues of International Journal of Molecular Sciences and Frontiers in Genetics BMC genomics. Now I joined Biophysical Reviews Editorial Board as IUPAB Councilor. I am a Secretary of National Committee of Russian Biophysicists, and have helped to organize scientific conferences and workshops, such as the VI Congress of Russian Biophysicists.

     

SOME STATISTICAL ASPECTS OF GEOGRAPHICAL DISTRIBUTION

I n recent discussions on the geographical distribution of animals and plants the subject has been approached from a novel point of view. An attempt has been made to investigate certain problems of distribution by the statistical or bio- metrical method; and it is thought by some that this method may throw new light, not only on the phenomena of distribution, but upon the general principles of biology, of which the facts of distribution must be in some degree the ex- pression*. There appear to be certain purely statistical aspects of the problems raised, which have so far been ignored; and since some of these considerations seem to be of a fundamental character, it is perhaps worth while to place them upon record. I advance these considerations with diffidence, because the points which I am about to make are in no way obscure; they are on the contrary very simple; and the only excuse for discussing them is that their fundamental im- portance for the statistics of distribution appears to have been overlooked.     

Phylogenetic relationships among laboratory and wild-origin Mus musculus strains on the basis of genomic DNA RFLPs

Genetic distance measures between the laboratory mouse strains C57BL/6J and RF/J and the wild-origin Mus musculus mouse strains CAST/Ei, MOLF/Ei, POSCH I, and CZECH II were estimated by allelic patterns revealed by RFLP analysis. These results suggest phylogenetic relationships indicating that the mouse strains related to the subspecies M.m. domesticus (RF/J, POSCH I and C57BL/6J) are more closely related to the CAST/Ei strain (derived from M.m. castaneus) than to the strains CZECH II (M.m. musculus) and MOLF/Ei (M.m. molossinus). Furthermore, the hybrid strain C57BL/6J is more closely related to POSCH I (M.m. poschiavinus) than to RF/J as calculated by the method distance measures of Cavalli-Sforza and Edwards (Evolution 21,550, 1967), Nei's minimum (Am. Natural. 106,283, 1972) and unbiased minimum (Genetics 89,583, 1978), Edwards (Biometrics 27,873, 1971; Genetic Distance, p. 41, 1974) and Rogers modified (1986).     

Bhattacharyya’s distance measure as a precursor of genetic distance measures

In Population Genetics, two populations are distinguished from each other on the basis of the differences in the distributions of the alleles at the locus or loci under consideration. These differences are measured by a “genetic distance” between the two populations (not to be confused with genetic distance between two loci, which is based on recombination fractions) and they play a major role in inferences at the population level. Several measures of genetic distance have been proposed by different authors (Sanghvi 1953; Cavalli-Sforza and Edwards 1967; Jukes and Cantor 1969; Nei 1972; Kimura 1980; Reynoldset al 1983; reviews in Felsenstein 1991; Nei and Kumar 2000). Most of these measures are actually dissimilarity measures and not mathematically true distance measures (B-Rao and Majumdar 1999). Independently, and much before the geneticists, statisticians too were concerned with the idea of distinguishing between two (statistical) populations. In order to discriminate between two populations on the basis of one or more characters, divergence measures like “Mahalanobis’D ² statistic” or “Mahalanobis’ generalized distance” (1936) and “Bhattacharyya’s distance” (1943, 1946), Kullback-Leibler’s divergence measure (1951) etc. have been proposed by statisticians. Mukherjee and Chattopadhyaya (1986) have mentioned measures based on distances, association between two attributes and discrimination function. There are similarities between the distance measures defined by applied scientists and by theoreticians. Felsenstein (1985) shows that three of the allele frequency-based genetic distance measures were anticipated by Bhattacharyya (1946). Nei and Takezaki (1994) have also studied the effectiveness of several genetic distance measures in the context of phylogenetic analysis, including Bhattacharyya’s distance measure.     

A simple completion of Fisher’s fundamental theorem of natural selection

Fisher''s fundamental theorem of natural selection shows that the part of the rate of change of mean fitness that is due to natural selection equals the additive genetic variance in fitness. Fisher embedded this result in a model of total fitness, adding terms for deterioration of the environment and density dependence. Here, a quantitative genetic version of this neglected model is derived that relaxes its assumptions that the additive genetic variance in fitness and the rate of deterioration of the environment do not change over time, allows population size to vary, and includes an input of mutational variance. The resulting formula for total rate of change in mean fitness contains two terms more than Fisher''s original, representing the effects of stabilizing selection, on the one hand, and of mutational variance, on the other, making clear for the first time that the fundamental theorem deals only with natural selection that is directional (as opposed to stabilizing) on the underlying traits. In this model, the total (rather than just the additive) genetic variance increases mean fitness. The unstructured population allows an explanation of Fisher''s concept of fitness as simply birth rate minus mortality rate, and building up to the definition in structured populations.     

The seasonal variation of airborne pollen grains that cause sugipollinosis in japan in the last three years

In Japan, the problems of Sugi (Cryptomeria japonica)-pollinosis have been much discussed in recent papers and journals. The author made an investigation on the airborne pollen grains from a scientific standpoint in connection with the incidence of pollinosis. By using the Cascade Impactor the author collected 600 liters of air sample a day, at the roof of the Pharmaceutical Science Building, Toho University, Funabashi, Chiba, Japan. Each air sampling for 2 hrs was repeated three times a week since 1969. The airborne pollen grains in each sample were counted under the microscope to identify the pollen types. The pollen grains were classified into six types according to the classification of pollen grains in Japan established by lkuse. The accumulated number of pollen of each species was analysed statistically by circular plot, Weibull plot, Edwards plot and semi-logarithmic plot. In this report mainly 3B type of pollen grains (Cryptomeria, Chamaecyparis), collected in the last three years are described. The total number of pollen grains in 1988 (2820 grains) was doubled in quantity as compared with that in 1987 (1177 grains) and in 1989 (1121 grains). The 3B type of pollen grains in 1988 (1450 grains) was 3.4 times as many as in 1987 (397 grains), and 12.9 times as in 1989 (112 grains). The 3B type of pollen grains represented the major portion of total pollen, and influenced the annual amount and the dispersal period.     

<Emphasis Type="Italic">MEFV</Emphasis> mutations in patients with familial Mediterranean fever from the Aegean region of Turkey

Familial Mediterranean Fever (FMF) which is frequently present in Mediterranean populations is caused by mutations in the MEFV gene. According to recent data, MEFV mutations are not the only cause of FMF, but these are major genetic determinants which cause FMF. It has also been suggested that there may be a number of other genes causing FMF. The MEFV gene is located at 16p13.3 and encodes a protein, pyrin/marenostrin. More than 70 disease associated mutations and totally 186 mutations and polymorphisms have been defined in affected individuals. We have retrospectively evaluated the molecular test results of 1,201 patients identified as having FMF clinical symptoms referred to the Molecular Genetics Laboratory of the Department of Medical Genetics, Faculty of Medicine, Ege University, Izmir/Turkey over the last 4 years. Patients were tested for 12 common mutations in the MEFV gene using a strip assay method (Innogenetics, Belgium). Out of the 1,201 patients tested (2,402 chromosomes) in the Aegean region in Turkey, 654 (54.45%) did not carry any mutations, among the 547 (45.55%) patients with mutations 246 patients were either homozygous (101) or compound heterozygous (145), 296 carried only one detected mutation, and five patients had three mutations. Allelic frequencies for the four most common mutations in the mutation positive groups were 47.60% (M694V), 16.75% (E148Q), 12.95% (V726A), 11.94% (M680I G/C).The remaining alleles (10.76%) showed rare mutations which were R761H, P369S, A744S, K695R, F479L, M694I. When the frequencies of mutations detected in our group were compared to the frequencies reported in the other regions of Turkey, an increase in V726A mutation frequency was observed. No patient showed a I692del mutation which is sometimes evident in other Mediterranean populations.     

Large sized nascent protein as dominating component during protein synthesis in Chironomus salivary glands

The main secretory protein fractions from Chironomus tentans have been investigated with particular emphasis on the dominant fraction, component 1, here designated I (Grossbach, 1969). This polypeptide was suggested to be the translatory product of 75 S RNA from Balbiani ring 2 (BR2) because of its size and quantitative prominence. Its molecular weight was estimated by gel filtration in 8 M urea at 850,000+101,000 D. During short pulses with radioactive amino acids a large fraction of the label was found in a population of polypeptide chains suggestive of molecules continuously growing to the size of component I. Populations of nascent large protein chains of similar size distribution were dominant in the polysomes and constituted the only population present in the largest polysomes, known to contain 75S RNA from BR2 (and BR1) as predominant or only component (Daneholt et al., 1977; Wieslander and Daneholt, 1977). These data indicate strongly that the large size of component I is not a result of posttranslational modifications. No sequence similarities, using limited proteolysis, were found between component I and component II, both of which have been considered to be BR2 products. There was, furthermore, no detectable immunological identity between component I and smaller secretory protein fractions. The data support Grossbach's and Daneholt's suggestion that component I is closely related to the primary translation product of 75S RNA from the large Balbiani rings.     

Chiasma formation in the short arm of the nucleolar chromosome of the tomato

Summary A translocation heterozygote in tomato (Lycopersicon esculentum) is shown to have a cyclical type of interchange between the long arms of chromosomes 1, 2 (nucleolar) and 3. A study of chromosome association in this plant at metaphase I has indicated that in 21% of the cells a ring of six chromosomes is present. Since an open ring hexavalent can occur only if there is chiasma formation in all the translocated segments and in all the short arms of the three chromosomes, it is concluded that there is considerable frequency of chiasma formation in the short arm of the nucleolar chromosome. This conclusion contradicts the previous observations that chiasma formation is either absent or very rare in the entirely dark staining chromatic, sometimes referred to as heterochromatic, short arm of the nucleolar chromosome.Part of this investigation was carried out at the Department of Genetics, Agricultural University, Wageningen, when the author was serving a contract between the EURATOM-I.T.A.L. and the Agricultural University.     

Increase of brain tryptophan and stimulation of serotonin synthesis by salicylate

I ndirect evidence indicates that the rate-limiting step in the synthesis of brain 5-HT is the concentration of tryptophan in brain and not, as previously considered (G reen and S awyer , 1966), tryptophan hydroxylase. In fact this enzyme has a K_m for its substrate much higher than the concentration of tryptophan normally present in the mammalian brain (J equier , L ovenberg and S joerdsma , 1967; J equier , R obinson , L ovesberg and S joerdsma , 1969; M cgeer , P eters and M cgeer , 1968). Tryptophan is the only amino acid circulating in plasma which is highly bound to serum proteins (M cmenamy and O ncley , 1958). We have previously shown that the free fraction of serum tryptophan controls the concentration of brain tryptophan and, therefore, 5-HT synthesis as well (T agliamonte , B iggio and G essa , 1971d; G essa , B iggio and T agliamonte , 1972). Salicylate has been shown to displace tryptophan from its protein binding in plasma and to raise the free tryptophan concentration (M carthur and D awkins , 1969; S mith and L akatos , 1971). These considerations prompted us to study the effect of salicylate on tryptophan concentrations and 5-HT metabolism in brain.     

A year since George Floyd

The murder of George Floyd sparked an awakening, long overdue, which reverberated throughout society. As science begins to acknowledge its role in perpetuating systematic racism, the voices of Black scientists, which have largely been absent, are now being called on. As we rightly begin to make space for diverse voices and perspectives in science, we all must think about what it is we are asking minoritized individuals to do.

It has been roughly 1 year since the murder of George Floyd, an unarmed Black man, who was killed over an alleged counterfeit 20 dollar bill in Minneapolis, Minnesota (Hill et al. 2020; Kaul, 2020; Levenson, 2021). In many ways, his murder was no different than the murders of thousands of other murders of Black people in this country (Thompson, 2020; Lett et al., 2021; Tate et al., 2021). However, what distinguishes George Floyd’s murder from many other high profile cases is that it was unambiguously captured on video (Alexander, 1994), an act of bravery by Darnella Frazier, a 17-year-old Black woman (Izadi, 2021), at a time when the world was mostly housebound by a raging global pandemic. As a result, his murder reverberated through society in a way that has not happened in my lifetime. While there have been other high profile cases of murders carried out by police (Treyvon Martin, Walter Scott, Breonna Taylor, and Philando Castile, among many others), these cases failed to fully sustain the attention of a national and international audience (Chan et al., 2020; Chughtai, 2021). The murder of George Floyd was fundamentally different, and for once, more than just Black people were paying attention. His murder sparked protests across the nation led by the Black Lives Matter (BLM) movement (Day, 2015; Taylor, 2016; Banks, 2018; Taylor, 2021), and the demands for change were so loud people could not help but hear.As a Black, gay man who is also a scientist, I was thrown into despair. All of my life I have thought if I just worked hard enough, if I am kind and unthreatening, if I play the game and keep my head down, maybe I can make it in academia. Maybe then I will be seen and accepted, not just by society, but by the scientific community. George Floyd’s murder reminded me, and many of my Black colleagues, that our degrees can’t protect us, that our privileged middle-class upbringing (if we had one) was not a shield. Our lives were not worth more than a counterfeit 20 dollar bill.Science, which has always been a product of society, was not impervious to these reverberations. By late June my inbox began to slowly fill with invitations to speak at several institutions for their seminar series, retreats, or special symposia. It felt as if the scientific community, for the first time, realized that there were Black scientists among them. In the throes of my own despair, and the feeling that I needed to be doing something for my community, I began to say “yes.” I was not going to participate in the nightly protests that occurred in my newly adopted hometown of Portland, Oregon. Aside from fearing I could be next to lose my life at the hands of the police (Edwards et al., 2019), these protests were happening in the backdrop of a global pandemic. I came to the conclusion that by accepting these invitations to speak, this could be my activism, my way of sparking change, increasing visibility, and being seen not only for my own sake but also for other Black scientists.Before I write anything else, I want to be clear: I am extremely thankful to all the institutions and organizations that invited me and gave me a platform. I am extremely proud of my students’ work and of the research we produce. I am sharing my experiences with the hope that they can be instructive to the greater scientific community, but if I am being frank, there is a bit of anger.I received over 15 invitations and gave an additional three or four interviews over the course of the year. Most of these came with the expectation that I would also talk about my work in Diversity, Equity, and Inclusion. But here’s the lowdown: prior to this year, I did not view myself as someone who did Diversity, Equity, and Inclusion work. I am co-chair of the LGBTQ+ committee of the American Society of Cell Biology and a member of the Diversity, Equity, and Inclusion committee of the Genetics Society of America. I volunteer for both of these committees because they speak to something I care deeply about, the advocacy for minoritized ¹ scientists. I also embody both of these axes of diversity; so, in some way, I am only looking out for myself. This is far from being a scholar or doing “Diversity work.” I fully recognize that there are individuals who have dedicated their lives to this type of work with entire academic fields populated with accomplished scholars. So, I started this year of talks being invited because I am a Black, gay scientist at a time when science was grappling with its own systematic racism, under the guise of my nonexistent Diversity, Equity, and Inclusion work.What has this year actually taught me? The first thing it taught me is that I have been missing out. Prior to George Floyd’s murder, I had only received three seminar invitations from major research institutions and unfortunately all within a year of being posttenure. That is after nearly 6 years in my current position.In giving these talks I got the opportunity to meet with some of the giants in my field, people I have looked up to for years. I received reagents, offers to collaborate, and a litany of great ideas that will help drive my research program for years to come. I left some of these meetings truly inspired and excited to start experiments. These opportunities would have been invaluable to me, pretenure. One could argue, I did not need it. I made it even without this networking and the advantages these visits bring. Before you applaud my ability to persist and be resilient, we should take a deep look at the systems that have forced people who look like me to be doubly resilient. If George Floyd had not been murdered, would any of these invitations have happened? If the previous 6 years are any indication of a trend, I would have to say most certainly not. Why did it take a murder and the reignition of a Civil Rights movement for me to have the type of interactions I now know many of my straight, white counterparts have had from the very beginning of their independent careers? Let me be clear: this is a form of systematic racism, plain and simple.As I began to make the rounds, I was often asked to either share a bit of my journey or include my Diversity, Equity, and Inclusion work in my talks. This sometimes came at the expense of sharing my lab’s work. While I was very happy to do so, this was very much implicit in the invitations I received. At times it did feel that my inclusion was only checking a box, placating the graduate students so that they could see that their department or institution was responding to their demands. This also had the consequence of making me feel as though my science was merely performative. I was being invited to do the Diversity work institutions did not want to do. This is the tension I, and many other minoritized scientists, face. I want to share my experiences with the hopes that the next generation will have it better; but, my scholarly work is not in Diversity, Equity, and Inclusion. I fully recognize that it is my embodied diversity that is bringing me to the table; but, it is the science I want to share.On the first invitation to give a seminar, I promised myself that I was going to be honest. This meant that I would tell the truth about my experience and bare my soul over and over again. What I had not counted on was the emotional toll this would take on me. Reliving my own trauma, on a regular basis, left me emotionally drained after these visits. In one of my “stops” (I use quotes here because these “visits” were all virtual), I met with the queer, person of color (POC), graduate students. This session quickly turned into an emotional support group where I heard stories of mistreatment, racism, and discrimination. It was nearly impossible to maintain my composure. Diversity, Equity, and Inclusion work is clearly extremely important, but, maybe, we could just start by listening to the needs of the students and having a bit of humanity.The trial of Derek Chauvin has come and passed, and much to my surprise, and to the surprise of many other Black people nationwide, he was found guilty and was sentenced to prison (Arango, 2021; Cooper and Fiegel, 2021). This, of course, is not justice, not even close. Justice would mean that George Floyd is still alive and would get to live out his life in the way he chose. We are also at the beginning of the end of the pandemic. In 6 months or less, we may all be returning to life, more or less, as it was before George Floyd, before COVID-19. Does this mean we stop fighting? Does this mean that I, and many other Black scientists, suddenly disappear? For George Floyd, for countless other faceless Black people before him, I sincerely hope not. We need to continue to give Black scientists a platform. We need to ensure that they, too, are given the opportunity to network, collaborate, and interact with the larger scientific community. This means the invitations cannot stop. To further this, we need to ensure that Black scientists are included in every grant review panel, are included on speaker lists at every national and international meeting, are funded, and are in the room where funding, tenure, and other critical decisions are being made. We need to recognize that systematic racism has not gone away with Derek Chauvin’s conviction and sentencing. We need to continue to push forward. And, for all of you young, minoritized scientists (and allies) reading this, demand change and do not take "no" for an answer. I am truly sorry this has fallen on your shoulders, but enough is enough. The next generation of minoritized scientists should be recognized for their science without the additional burden of creating their own space.About the AuthorI am currently an Associate Professor of Biology at Reed College (https://www.reed.edu/biology/applewhite/index.html), which is located in Portland, Oregon. I arrived at Reed in 2014; prior to that, I was a postdoctoral fellow at the University of North Carolina, Chapel Hill. I received my PhD from Northwestern University in Cellular and Molecular Biology and a BS in Biology from the University of Michigan where I was also a 4-year letter winner in track and field. My research focuses on the cytoskeleton where I study cell motility and morphogenesis using Drosophila and Drosophila derived in tissue culture cells to explore actin, microtubules, and molecular motors. My current lab is composed of fierce, determined undergraduate students. I am a member of the American Society of Cell Biology (ASCB) and the current chair of the LGBTQ+ Committee (https://www.ascb.org/committee/lgbtq/). I am also a member of the Diversity, Equity, and Inclusion Committee for the Genetics Society of America (https://genetics-gsa.org/committees/). I also serve as an editor for MBoC’s Voices series.     

Gene targeting by homologous recombination: a powerful addition to the genetic arsenal for Drosophila geneticists

A series of recent publications have firmly established the notion that Drosophila researchers now have a general method to subject genes for targeted modification by homologous recombination (HR) [Science 288 (2000) 2013; Genetics 157 (3) (2001) 1307; Genes Dev. 16 (12) (2002) 1568; Genetics 161 (2002) 1125-1136]. This method allows one to knockout essentially any gene starting with the DNA sequence of the gene. It has greatly enhanced studies of gene function as demonstrated by over 20 years of gene targeting practice in yeast and mouse. Here, I discuss the basic targeting methodology for eukaryotic organisms. I compare the Drosophila method with the traditional targeting scheme in yeast and mouse mainly to show that the targeting mechanism as well as many aspects of the experimental design remain unchanged, and that the Drosophila scheme differs only in the way in which the donor molecule for targeting is generated. I propose that the Drosophila method can be readily adapted in other organisms without culturable stem cells, since the mechanism for in vivo donor generation in Drosophila is likely to be functional in a variety of different organisms.     

Screening for minute deletions in patients with suspected cri-du-chat syndrome and apparently normal karyotype

Summary Measurement studies were carried out on the B-group chromosomes in three patients with suspected cri-du-chat syndrome, four karyotypically confirmed cases of the syndrome and three normal subjects. None of the propositi showed a detectable short-arm deletion. Within the four cases with obvious short arm deletion the amount of the deletion varies to a high degree. In addition to the technique of chromosome measurement proposed by other authors (e.g. Warburton et al., 1967, 1969; Miller et al., 1969), we present another method easely to apply for screening purposes in cases in which a deletion is not readily detectable, blind studies were unsuccessful, or when the amount of the deletion ought to be demonstrated.

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Zusammenfassung Messungen der B-Chromosomen wurden in Metaphasen verschiedener Probanden durchgeführt: 1. drei Patienten mit Verdacht auf Cri du Chat-Syndrom ohne sichtbare Defizienz am kurzen Arm von Chromosom 5; 2. vier Patienten mit deutlich erkennbarer Defizienz; 3. drei gesunde Vergleichspersonen mit unauffälligem Karyotyp. Eine Deletion war in keinem der Verdachtsfälle nachweisbar. In der Gruppe mit Defizienz zeigte sich eine erhebliche Variation im Ausmaß des deletierten Segments. In Ergänzung zu Methoden der Chromosomenmessung anderer Autoren (vgl. Warburton et al., 1967, 1969; Miller et al., 1969) wird eine weitere einfache Methode angewendet, die unter geringem Aufwand in Zweifelsfällen Aufschluß über das Vorhandensein und Ausmaß einer Deletion am kurzen Arm eines B-Chromosoms geben kann.