Invited Speakers 1-C What we did and what we do J. Egozcue Professor Emeritus of Cell Biology, Universitat Auto© nomade Barcelona, Spain To commemorate the 50th anniversary of the ¢rst accurate description of the human chromosome num- ber, I will try to put into perspective the technologies used in the earlier years, and the ones which are available to us nowadays. First, I will pay a tribute to some of our predecessors, such as T.S. Painter, who established that our 2n was 46, to later change his mind to 48, with some unexpected consequences, or Elisabeth H. Slifer, who ¢rst tried the e¡ects of anisotonic solu- tions to improve chromosome spreads. Then, we will reach 1953 and the hypotonic miracle, which allowed Tjio and Levan to con¢rm our 2n at 46, contempor- aneously with Ford and Hamerton, who reached the same conclusion using testicular material. Finally, we will browse the developments which have taken place in three cytogenetics ¢elds which I have chosen for reasons of a¤nity: chromosome evolution, the cytogenetics of reproduction and the cytogenetics of hematological neoplasias. My lecture will try to demonstrate that, in spite of the spectacular developments of molecular biology, the chromosome, as the support of all activities which take place in our genome, will always be the essential element to map, de¢ne, correlate, interpret and understand any genetic process. 2-C Clinical ¢ndings in autosomal chromosome aberrations A. Schinzel University of Zurich, Institute of Medical Genetics, Switzerland Autosomal chromosome aberrations are accompanied by a characteristic phenotype which includes, as major features, a pattern of minor dysmorphic signs, a pattern of major organ malformations, mental de¢ciency and impaired growth both pre- and postnatally. Many aber- rations are associated with a speci¢c behavioural pro¢le. Further characteristic ¢ndings include diminished and delayed puberty and thus a long period of growth and early senescence. If a deletion includes a gene with haploinsu¤ciency, chromosome aberrations may also show features of dominant or X-linked conditions. Malformations frequently present in chromosome aber- rations are those which are common in general and, if present as isolated ¢ndings, usually follow multifactorial inheritance.Dysmorphic¢ndingsmainlyconcernfacies, genitalia and distal limbs and undergo marked changes with age. A review of further characteristic of autosomal chro- mosome aberrations will be presented. 3-C Autosomal imbalance and copy number variation without phenotypic e¡ect J. Barber Wessex Regional Genetics Laboratory, UK Directly transmitted cytogenetically visible anomalies can be divided into unbalanced chromosome abnormal- ities (UBCAs) and euchromatic variants (EVs). UBCAs involve heterozygous single copy number changes of segments larger than 2 Mb that do not vary in the normal population. Among 130 UBCA families, most of the UBCAs were unique to each family and 77/ 130 (58%) were associated with a consistently mild phenotype. In 30/130 (23%) families, the a¡ected pro- band had the same UBCA as other normal family members. In 23/130 (18%) families, ascertained mostly at prenatal diagnosis, UBCAs with an average size of almost 10 Mb had no detectable phenotypic e¡ect. Regions of low gene density were involved in 3 of the 4 UBCAs reported in more than one normal family. All the established cytogenetic EVs of 8p23.1, 9p12, 9q12, 15q11.2 and 16p11.2 have been described in multiple independent families and most involve copy number variation of paralogous gene and pseudogene cassettes of less than 2Mb; these are polymorphic in the normal population and only reach the cytogenetic level when copy number is high. These EVs do not have signi¢cant phenotypic consequences and the co-segrega- tion of an EV with mild phenotypic anomalies in 2/70 (3%) families was thought to be coincidental. However, EVs may yet be found to a¡ect traits which show continuous variation. The 200 UBCA and EV families form the `Chromo- some Anomaly Collection' at http://www.ngrl.org.uk/ Wessex/register. Further close collaboration between medical and laboratory sta¡ will be essential to distin- guish clinicallysilent variation from pathogenic rearran- gement. ChromosomeResearch.2005; 13 (Supplement 1):1^16. # 2005 Springer.PrintedintheNetherlands