Biomedical subjects

Joseph F Williamson

Publications and source records attributed to Joseph F Williamson.

3 recordsLinked to original sources

PubMed2005

Extensive genomic and functional polymorphism of the complement control proteins.

Using combinations of genomic markers, we describe more than 20 distinct ancestral haplotypes (AH) of complement control proteins (CCPs), located within the regulators of complement activation (RCA) alpha block at 1q32. This extensive polymorphism, including functional sites, is important because CCPs are involved in the regulation of complement activation whilst also serving as self and viral receptors. To identify haplotypes, we used the genomic matching technique (GMT) based on the pragmatic observation that extreme nucleotide polymorphism is packaged with duplicated sequences as polymorphic frozen blocks (PFB). At each PFB, there are many alternative sequences (haplotypes) which are inherited faithfully from very remote ancestors. We have compared frequencies of RCA haplotypes and report differences in recurrent spontaneous abortion (RSA) and psoriasis vulgaris (PV).

Amino Acid Sequence↗

PubMed2004

Amino acid patterns within short consensus repeats define conserved duplicons shared by genes of the RCA complex.

Complement control proteins (CCPs) contain repeated protein domains, short consensus repeats (SCRs), which must be relevant to diverse functions such as complement activation, coagulation, viral binding, fetal implantation, and self-nonself recognition. Although SCRs share some discontinuous and imperfect motifs, there are many variable positions and indels making classification in subfamilies extremely difficult. Using domain-by-domain phylogenetic analysis, we have found that most domains can be classified into only 11 subfamilies, designated a, b, c, d, e, f, g, h, i, j, or k and identified by critical residues. Each particular CCP is characterized by the order of representatives of the subfamilies. Human complement receptor 1 (CR1) has ajefbkd repeated four times and followed by ch. The classification crosses CCPs and indicates that a particular CCP is a function of the mix of SCRs. The aje set is a feature of several CCPs including human CR1 and DAF and murine Crry and appears to be associated with the success or failure of implantation inter alia. This approach facilitates genomic analysis of available sequences and suggests a framework for the evolution of CCPs. Units of duplication range from single SCRs, to septamers such as efbkdaj, to extensive segments such as MCP-CR1L. Imperfections of duplication with subsequent deletion have contributed to diversification.

Amino Acid Motifs↗

PubMed2003

In polymorphic genomic regions indels cluster with nucleotide polymorphism: Quantum Genomics.

Previously, we have described polymorphic frozen blocks (PFBs) within the Major Histocompatibility Complex (MHC) as regions of several hundred kilobases characterised by high nucleotide diversity, little or no recombination, duplicated segments, disease susceptibility, and human endogenous retroviruses. The nucleotide diversity profile within these PFBs shows peaks and troughs outside of the Class I genes, reflecting other important genes (or sequences) in the region. Here we show that indel density is also clustered with similar peaks and troughs. In fact, SNPs and indels are co-located within PFBs.

Databases, Nucleic Acid↗