Alignment in Complex Genomic Regions

Developing artificial chromosomes reference panels for alignment in complex regions of the human genome


Certain regions of the human genome are extremely repetitive and/or complex (e.g the cone opsin region on chromosome X) and are currently inadequately captured by the human genome build.

These regions prove very challenging to align using commonly used short read sequencing techniques and traditional alignment algorithms. Genetic disease mechanisms may be missed in exome, genome and RNAseq datasets using the current reference sequence and genome builds.

We propose to investigate novel ways of providing more current and bespoke builds to assess inherited retinal diseases caused by mutations, including interchange haplotypes, in the cone opsin array. These methods could then be applied to assess the impact of structural variants and interchromosomal insertions that have been implicated as disease causing.

Skills and Techniques to be used

  • Gain deep understanding of NGS data formats, fastq data, quality control, genome builds and alternative scaffolds.
  • Understanding of the theory of alignment algorithms such as Burrow-Wheeler Aligner.
  • Command line Linux bioinformatics skill for alignment of complex sequence rearrangements.
  • Investigate novel approaches to alignment such as graph based alignment.


  1. Three different cone opsin gene array mutational mechanisms with genotype-phenotype correlation and functional investigation of cone opsin variants. Gardner JC, Liew G, Quan YH, Ermetal B, Ueyama H, Davidson AE, Schwarz N, Kanuga N, Chana R, Maher ER, Webster AR, Holder GE, Robson AG, Cheetham ME, Liebelt J, Ruddle JB, Moore AT, Michaelides M, Hardcastle AJ. Hum Mutat. 2014 Nov;35(11):1354-62. doi: 10.1002/humu.22679. PMID: 25168334
  2. X-linked cone dystrophy caused by mutation of the red and green cone opsins. Gardner JC, Webb TR, Kanuga N, Robson AG, Holder GE, Stockman A, Ripamonti C, Ebenezer ND, Ogun O, Devery S, Wright GA, Maher ER, Cheetham ME, Moore AT, Michaelides M, Hardcastle AJ. Am J Hum Genet. 2010 Jul 9;87(1):26-39. doi: 10.1016/j.ajhg.2010.05.019. Epub 2010 Jun 24. PMID: 20579627


Nikolas Pontikos

Principal Investigator

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We are always eager for hard-working & motivated people to come and work with us.

If you're interested in joining us, please send Nikolas Pontikos a quick email with a CV and personal statement