RECORD NO.:  95329615
       AUTHOR:  Dallapiccola B; Mingarelli R; Novelli G
      ADDRESS:  Cattedra di Genetica Umana Universita Tor Vergata di Roma e 
                Ospedale, Generale Regionale CSS, San Giovanni Rotondo, 
                Rome, Italy.
        TITLE:  The link between cytogenetics and mendelism.
       SOURCE:  Biomed Pharmacother (A59), 1995; 49 (2): 83-93
     LANGUAGE:  English
 COUNTRY PUB.:  FRANCE
 ANNOUNCEMENT:  9510
    PUB. TYPE:  JOURNAL ARTICLE; REVIEW; REVIEW, TUTORIAL
 NUMBER REFS.:  65
     ABSTRACT:  High resolution chromosome analysis, molecular cytogenetics, 
                and study of the association between specific chromosome 
                rearrangements and single gene disorders have provided a 
                chromosomal basis to a number of mendelian diseases. 
                Deletions and duplications of small regions, usually less 
                than 3 Mb in size, result in an alteration of normal gene 
                dosage of a number of unrelated genes physically close to 
                each other and are responsible for contiguous gene 
                syndromes. For example, haploinsufficiency is implicated for 
                del 8q24.1 in Langer-Giedion syndrome, del 17p13.3 in Miller-
                Dieker syndrome, and del 22q11.2 in DiGeorge and Velo-
                cardiofacial syndromes. Another chromosomal mechanism 
                causing mendelian phenotypes is translocation, which may 
                eventually interrupt a disease gene. It is assumed that 
                translocation breakpoints are running through a relevant 
                gene, hindering the production of the gene product. An 
                example is breakage 16p13.3 associated with Rubinstein-Taybi 
                syndrome. Females with X/autosome translocations have an 
                almost exclusive inactivation of the normal X. Interruption 
                of a disease gene in the translocated X causes the 
                expression of a mendelian phenotype in the presence of an 
                allelic recessive mutation onto the nonrearranged X. 
                Finally, if a human gene shows exclusive expression from a 
                single parental homologue, ie, it is imprinted, deletion of 
                the chromosomal segment containing the active allele results 
                in structural monosomy and functional nullisomy. This 
                situation is illustrated by Prader-Willi and Angelman 
                syndromes. Over seventy human genes have been precisely 
                assigned to chromosomal regions using a cytogenetic 
                approach. Chromosome techniques combined with molecular 
                methods have proved to have powerful and sensitive 
                diagnostic capabilities.
MESH HEADINGS:  *Chromosome Deletion; *Cytogenetics; Chromosome Mapping; 
                Gene Rearrangement; Genomic Imprinting; Linkage (Genetics); 
                X Chromosome; Female; Human; Male; Support, Non-U.S. Gov't
 STANDARD NO.:  0753-3322
        DATES:  Entered 950817