Programme MaNaMa Day 2

                                                                                    Genome diagnosis

11/10/23 - UZ Gent

Coordinator: Bruce Poppe

Teachers: Sofie Symoens & Annelies Dheedene

Location: UZ Gent campus, MRB2, entrance 38, campus UZ Gent.


• 9:30 – 10:30

Cytogenomic technologies for constitutional and acquired disorders: karyotyping, FISH, QF-PCR, 

shallow whole genome sequencing and microarray (CGH and SNP), NIPT (Annelies)

• 15’ break

• 10:45 – 12:15

Gene panel analyses (targeted/customized gene panels) (Sofie) 

Whole exome and whole genome sequencing (Annelies)

PGT-SR and PGT-A (Annelies)

PGT-M, coPGT, BeGECS and carrierships (Sofie)

• 45’ lunch

• 13:00 – 14:15

Variant classification for constitutional and acquired diseases (Sofie & Annelies)

• 15’ break

• 14:30 – 16:00

Educational cases and illustrations of genetic reports

• 15’ break

• 16:15 – 18:00

Exercises: interpreting and reporting genetic analyses

Aims/learning objectives

- How to write and read a clinical genetic report

- The student knows and is able to use in silico tools for genome analysis in clinical genetics.

- The student will learn the principles of variant classification

What you need to know before taking this course:

haploinsufficiency, dominant negative, gain-of-function, different types of variants


  • Sources of genetic material

Sources and extraction of RNA, DNA, protein, mitochondrial DNA, fibroblast culture, EBV, ..

  • Sequencing: from DNA to raw data to the variant list

- The basis of some techniques are illustrated with the aim to understand how already in these first stages certain mutations may be missed

- Types of variants that can be retrieved from exome/genome (e.g. SNV, CNV, other structural variation, microsatellites, …)

- nomenclature of variants (deletions, insertions, etc.)

  • Variant interpretation

            o In silico 


           Genome Browser: ensembl and UCSC Protein structure databases

           Mutation databases: Clinvar, LOVD, other databases Normal variation databases: gnomAD

Variant classification

           ACMG rules for variant classification

           In silico prediction programs

           classification incorporating phenotypic information – HPO terminology

           o In vivo: segregation analysis 

Clinical databases

           Orphanet, GeneReviews, OMIM, Pubmed, … 

           Data sharing: Decipher, Genematcher

           o In vitro

Functional: splicing, structure of proteins