Module 1: Lesson 2 – Patterns of Genetic Inheritance

Trainers

Name: Shareefa Dalvie
Affiliation: University of Cape Town
Location: Cape Town, South Africa

I was born and raised in Cape Town, South Africa. In 2007, I completed my Bachelor of Science degree, majoring in Genetics & Development and Physiology, at the University of Cape Town (UCT). Thereafter, I completed my honours, masters and doctoral degrees at the Division of Human Genetics at UCT. From 2015 to 2016, I held a Brain-Behaviour Initiative (BBI) postdoctoral fellowship at the Department of Psychiatry and Mental Health. I am currently a lecturer at the Department of Psychiatry and Mental Health and co-head the Psychiatric Neurogenetics group of the Brain-Behaviour Unit (BBU). My research interests include the genetic basis of trauma exposure in individuals with post-traumatic stress disorder (PTSD) using genome-wide association (GWAS) data, population structure and gene-imaging analyses.

Name: Prof Guida Landoure
Affiliation: Université de Sciences, des Techniques et des Technologies de Bamako
Location: Mali, Bamako

Guida Landouré is a medical doctor trained in general medicine in Mali in 2002. He joined the National Institutes of Health (NIH) through the exchange visitor program in 2004 where he stayed until the end of 2007 before joining the University College London, London, UK in 2008 as research assistant. At the same time, he undertook a PhD thesis which he successfully defended in 2011. Dr. Landouré  is now Assistant Professor in Neurology at the University of Sciences, Techniques and Technology of Bamako, Mali, and has settled a Laboratory working on neurogenetics diseases and . Dr. Landouré’s work is focused on hereditary neurological disorders but also other genetic disorders afflicting the African population such as sickle cell disease. His work has led to the characterization of new clinical entities, and the discovery and characterization of the gene for several neurological diseases. He is a member of several scientific communities in Africa and abroad. His short-term research goal is characterize hereditary neurological disorders and establish their molecular basis. His long-term research goal is to implement molecular diagnosis in West Africa as to make it a standard practice and capacity-building to close the existing gap between Africa and the rest of the world in terms of genetic research and healthcare delivery.

Summary
The course aims to familiarize participants with basic genetic concepts and terms with a particular focus on Mendelian and non-Mendelian forms of inheritance patterns. At the end of the course, participants should be able to draw and interpret a pedigree. Mendelian (autosomal, X and Y-linked) and non-Mendelian transmission patterns (mitochondrial, genomic imprinting, mosaicism, etc) will be taught with examples of disorders given for each type of pattern. Multifactorial/complex disorders with environmental components will be described briefly.

Learning Outcomes

  • Explain basic genetics terms in simple language to patients
  • Explain the interplay between genetics and environment
  • Identify instances of Mendelian and non‐Mendelian inheritance
  • Record and interpret a family history, recognising what is or may be relevant
  • Apply family history to draw pedigrees and determine mode of inheritance of a genetic disease

Class Videos
Module1_Lesson1_Video1_Landoure-Dalvie

Module1_Lesson2_Video2_Landoure-Dalvie

Module1_Lesson2_Video3_Landoure-Dalvie

Class Slides
Module1_Lesson2_Slides_Landoure&Dalvie

Assessments: Preclass exercise
Reading 1 – Genetic inheritance Credit to University of Utah Genetic Science Learning
Reading 2 – Family Pedigree Credit to Mark Drollinger
Reading 3 – Blood Groups

Think of instances where you have observed a family where some of the members have an inherited disease or a condition such as Albinism. Explain the relationships between the family members indicating members who are symptomatic of the disease. Explain why you are interested in this case or aspects about the disease/condition you did not understand. Write this summary load onto Vula (Please do not include real names or locations for patient privacy).

Assessments: Class Exercise
Question 1: Mrs T, a 33-year-old mother, walks in with her 1-year-old girl for walking delay. Pregnancy and delivery were unremarkable. She sat at 8 months but never crawled and cannot stand neither can she walk. Family history revealed that she has 3 other children (10 and 7-year-old girls and a 5-year-old boy) who had similar problems. None of them are able to walk. She has an older daughter (14 years) free of symptoms. Mrs. T is married to a cousin. Their mothers are cousins (the mother of his husband is the daughter of the older brother of her maternal grandmother). Mrs. T has 4 unaffected younger brothers. No other relatives have had these symptoms.
a. Please draw the pedigree of this family.
b. What is the pattern of the inheritance?
3=c. Mrs. T wanted to have another child and wanted to know the chances that she/he will have the disease in the family. What would you tell her in simple language?

Question 2: Mrs S., a 25-year-old female from a consanguineous marriage (her father’s mother is the older sister of her mother’s father) and mother of a 6-year-old girl, was referred from her dentist to the neurology department because of slurred speech and head tremor. On examination, in addition to the symptoms above, she has walking difficulties. Symptoms started age 20. During examination she signaled other affected relatives: her mother, maternal grandmother, maternal great grandfather, an older maternal aunt who also has an affected daughter of 42 and an unaffected son of 40, a younger maternal uncle, and an older sister of 38. On the other hand she has a twin brother and sister of 40 and an older sister of 34, all unaffected. She reports losses of two siblings, a brother who would be 42 today and a sister who would be 36 today.
a. Please draw the pedigree.
b. Is this Mendelian?
c. What is the pattern of inheritance in family and what differentiates it from the others? Name a disorder for the other patterns of inheritance you know.

Question 3. What are the chances that the daughter of the proband will show symptoms?

Question 4. The Facilitator to choose one or two examples from the pre-class exercises and ask the class to draw a pedigree from this examples/examples. This can be loaded onto Vula.

Quiz
Click to assess quiz questions

Class Evaluation
See course evaluations section.

This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.

Extra Readings
https://ghr.nlm.nih.gov/primer/inheritance/inheritancepatterns Credit – National Library of Medicine (US). Genetics Home Reference [Internet].

Thompson & Thompson: Genetics in Medicine, 7th Edition