RESUMEN
A large collection of good genetic markers is needed to map the genes that cause human genetic diseases. Although nearly 400 polymorphic DNA markers for human chromosomes have been described, the majority have only two alleles and are thus uninformative for analysis of genetic linkage in many families. A few known marker systems, however, detect loci that respond to restriction enzyme cleavage by producing a fragment that can have many different lengths. This polymorphism is due to variation in the number of tandem repeats of a short DNA sequence. Because most individuals will be heterozygous at such loci, these markers will provide linkage information in almost all families. Ten oligomeric sequences derived from the tandem repeat regions of the myoglobin gene, the zeta-globin pseudogene, the insulin gene, and the X-gene region of hepatitis B virus, were used to develop a series of single-copy probes. These probes revealed new, highly polymorphic genetic loci whose allele sizes reflected variation in the number of tandem repeats.
Asunto(s)
Mapeo Cromosómico , Secuencias Repetitivas de Ácidos Nucleicos , Cromosomas Humanos/análisis , Cósmidos , Enzimas de Restricción del ADN/metabolismo , Genes Virales , Globinas/genética , Virus de la Hepatitis B/genética , Humanos , Linaje , Polimorfismo GenéticoAsunto(s)
Aneuploidia , Mapeo Cromosómico/métodos , Enzimas de Restricción del ADN , Polimorfismo Genético , Aborto Espontáneo/genética , Antígenos de Grupos Sanguíneos/genética , Cromosomas Humanos 16-18 , Femenino , Humanos , Meiosis , Embarazo , Aberraciones Cromosómicas Sexuales/genética , TrisomíaAsunto(s)
Venenos Elapídicos/metabolismo , Receptores Muscarínicos/metabolismo , Sinaptosomas/metabolismo , Secuencia de Aminoácidos , Animales , Unión Competitiva , Encéfalo/metabolismo , Secuencia de Consenso , Venenos Elapídicos/química , Venenos Elapídicos/toxicidad , Elapidae , Cobayas , Íleon/efectos de los fármacos , Íleon/fisiología , Técnicas In Vitro , Cinética , Datos de Secuencia Molecular , Contracción Muscular/efectos de los fármacos , Músculo Liso/efectos de los fármacos , Músculo Liso/fisiología , N-Metilescopolamina , Parasimpatolíticos/metabolismo , Pirenzepina/análogos & derivados , Pirenzepina/metabolismo , Unión Proteica , Ensayo de Unión Radioligante , Receptores Muscarínicos/efectos de los fármacos , Derivados de Escopolamina/metabolismo , Homología de Secuencia de Aminoácido , PorcinosRESUMEN
The parental origin of the single X chromosome in sex-chromosome monosomy was evaluated by comparing restriction fragment length polymorphisms (RFLPs) of 10 spontaneous aborted 45,X conceptions with those of their parents. Seven X-linked marker loci were used, and we were able to specify the origin of the X in nine cases, with six being maternally and three paternally derived. These results demonstrate the efficiency of the technique and show that the single X chromosome in 45,X spontaneous abortions can be derived from either parent.
Asunto(s)
Deleción Cromosómica , Monosomía , Cromosoma X , Aborto Espontáneo/genética , ADN/genética , Enzimas de Restricción del ADN , Femenino , Ligamiento Genético , Marcadores Genéticos , Humanos , Masculino , Hibridación de Ácido Nucleico , Padres , Polimorfismo Genético , EmbarazoRESUMEN
Structure-related inhibitory effects on the prostaglandin synthesis in vitro have been detected among eight diterpenoids of the cembrane class (1-8). The 4,6-diols 1 and 2 are the most active of the cembranoids studied with IC50 values of 0.36 and 0.39 mM, respectively, as compared with an IC50 value of 1.4 for acetylsalicylic acid. Lower activities are found for cembranoids having undergone oxidation of/at the 11,12 double bond (5-8), while the 4-hydroxy-6-oxocembranoids 3 and 4 exhibit effects lower than those of 1 and 2 but higher than those of 5-8.
Asunto(s)
Diterpenos/química , Nicotiana/química , Plantas Tóxicas , Prostaglandinas/biosíntesis , Animales , Bovinos , Estructura Molecular , Relación Estructura-ActividadRESUMEN
The polymorphic locus D19S11 consists of four closely linked RFLPs: alpha, beta, delta, and gamma on chromosome 19p13.2----19cen, revealed by subclones p13-1-82 and p13-2-21 from cosmid 1-13. Here, we report that p13-1-25, an additional subclone of c1-13, reveals three insertion/deletion RFLPs, alpha, epsilon, and phi, at the D19S11 locus. In situ hybridization of p13-1-25 to metaphase chromosomes from a carrier of a 19/X translocation with a breakpoint near the centromere confirms localization of D19S11 to 19p. Studies with hydatidiform moles have generated assignments of specific restriction fragments to these three loci, and genotypic studies in three-generation families have indicated that they are closely linked. Loci alpha (also detected by p13-1-82) and phi each have but two common alleles, whereas epsilon has at least 33 alleles, including a null allele. Fifty unrelated individuals tested displayed unique fragment patterns on Taq I blots probed with p13-1-25. Applications of this probe include monitoring loss of chromosome 19 during tumorigenesis, monitoring engraftment of donor bone marrow after transplantation, testing for paternity, and mapping disease genes on chromosome 19.
Asunto(s)
Mapeo Cromosómico , Cromosomas Humanos Par 19 , Ligamiento Genético , Polimorfismo Genético , Polimorfismo de Longitud del Fragmento de Restricción , ADN/genética , Femenino , Marcadores Genéticos , Humanos , Cariotipificación , Masculino , Linaje , Translocación GenéticaRESUMEN
A primary genetic map for human chromosome 12 has been constructed from data on 23 restriction fragment length polymorphic systems collected in 38 normal families with large sibships. Linkage analysis of the genotypic data has ordered 16 loci into a continuous genetic map of 111 cM in males and 258 cM in females. Although most of the genetic map reflects a higher rate of recombination in females relative to males, significantly more frequent recombination was observed in males than in females in intervals between loci on the distal portion of the short arm of the chromosome. The mapping data shown here will serve as a first step toward a high-resolution genetic map for human chromosome 12.