Charlotte Gonther

Master’s Thesis in collaboration with Hannover Medical School
Title: The role of SNPs in telomere regulation in Sudden Infant Death Syndrome (SIDS)

Sudden Infant Death Syndrome (SIDS) describes the unexplained death of an infant under one year of age which appears to be healthy, and where the cause of death remains unexplained after a complete postmortem investigation. The most common feature in this regard is that the death mostly occurs during sleep. The so-called “triple-risk model” suggests that infants are at increased risk of dying from SIDS when three factors coincide: a vulnerable infant, a critical developmental phase, and exogenous stressors. It forms the basis for various explanatory approaches to pathogenesis, which focus in particular on pathological changes in the brainstem (brainstem hypothesis), cardiac pathologies, and the link between infections and the immune system. Nevertheless, despite decades of research, the exact aetiological mechanism remains unknown. Telomeres are the end caps of human chromosomes that ensure their protection and the integrity of their DNA throughout cellular division. They act as a buffer to protect and prevent the loss of essential genetic information during DNA replication, which enables cellular replication throughout life. This process involves a combination of protective proteins known as the shelterin complex and the telomerase complex. The shortening of telomeres is a normal age-related process, however, it can be influenced by external factors or genetics. Inherited telomere biology disorders (TBD) are characterised by impaired telomere maintenance, abnormal telomere lengths and/or telomere dysfunction, which can result in a wide range of diseases.
A possible link between telomere dysfunction and SIDS has so far remained largely unexplored, which is why further characterisation is to be carried out in this study. The first part of the thesis will consist of a literature review to identify genes that influence telomere length. Subsequently, a bioinformatic analysis will be performed using sequencing data from 144 SIDS cases, obtained from a whole-genome sequencing (WGS) dataset from the Seattle Children's Research Institute (Washington, USA; Bard et al. 2024), to identify single nucleotide polymorphisms (SNPs), as well as insertions and deletions (Indels) that are associated with SIDS. In the second part of the thesis, genetic mutations identified during the bioinformatic analysis of the data from Seattle are to be investigated using molecular genetic methods in the Hannover Medical School’s SIDS sample collection.
Overall, the aim of the thesis is to characterise previously unknown telomere associated SNPs and Indels that may contribute to the aetiology of SIDS.



Bard AM, Clark LV, Cosgun E, Aldinger KA, Timms A, Quina LA, Lavista Ferres JM, Jardine D, Haas EA, Becker TM, Pagan CM, Santani A, Martinez D, Barua S, McNutt Z, Nesbitt A, Mitchell EA, Ramirez JM (2024) Known pathogenic gene variants and new candidates detected in sudden unexpected infant death using whole genome sequencing. American Journal of Medical Genetics 194A:e63596