Function genetic mutations

Loss-of-function mutations in members of the Neuroligin (NL) family of trans-synaptic cell adhesion molecules have been implicated in human autism and mental retardation (Chih et al., 2004 Comoletti et al., 2004 Jamain et al 2003 Laumonnier et al., 2004 Yan et al, 2005). At the time of writing, neuroligin mutations represent owe of only a few independently replicated, functional, genetic mutation links to idiopathic autism not associated with a broader neuropsychiatric syndrome (Chih et al., 2004 Comoletti et al., 2004 Jamain et al., 2003 Laumonnier et al., 2004 Yan et al., 2005). 

Mutagens Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes. [NIH]... 

Lucchesi JC (1968) Synthetic lethality and semi-lethaHty among functionally related mutations of Drosophila melano aster. Genetics 59 37-14... 

During heart failure (HF), functional expression of different proteins involved in E-C coupling is altered, and these changes contribute to altered Ca transients, contractility and arrhythmias in HF. Furthermore, genetic mutations in the key Ca-cycling proteins have been recently identified, which contribute to heart failure and fatal arrhythmias. This chapter will concentrate in recent studies on genetic modifiers of cardiac function at the level of the sarcoplasmic reticulum. 

BH4 responsiveness has led Dr. Blau to create a functional database for the PAH molecule in which individuals can contribute to the functional mapping of genetic mutations (http // www.bh4.org). 

An interesting correlation between tripeptide sequences and genetic mutations has been made by compilation of the number of occurrences of the tripeptide sequence Asn—B—Ser and Asn—B—Thr in protein sequence-data at present available from the literature.134 A total of 18,251 tripeptide sequences from 264 proteins was grouped by computer into the 400 possible tripeptide combinations of the 20 amino acids in which the second position was ignored. The total number of Asn—B—(Ser/Thr) sequences actually present in these proteins was 61, whereas the total number theoretically expected, on the basis of a random distribution within the sequence, would have been 102. The observed data were thus lower than expected by 4 standard deviations. On the other hand, such chemically similar tripeptides as Gin—B—(Ser/Thr), Asp—B—(Ser/Thr), and (Ser/Thr)—B—Asn occurred the number of times expected for random distribution. It was suggested that this low frequency of incidence of the Asn—B—(Ser/Thr) sequence results from a restriction of its occurrence in proteins by a process of natural selection. Any protein that acquired this tripeptide as a result of a mutation would be soon rejected, because carbohydrate would be bound to the asparagine residue and its presence would interfere with the normal metabolic function of the protein. 

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