Lecture 5: Developmental Genetics of the Human Brain Flashcards
When does the development of neurons occur?
the first and second trimester
When does the development of astrocytes and oligodendrocytes?
during the third trimester and the first year of life
expansion of the glial cells, astrocytes and oligodendrocytes is dependent upon the pool of remaining neuronal progenitors and neuronal activity
When are the first neuronal circuits established?
established in the embryo shortly after neurons are born
When are cerebral cortical areas established?
during the fetal period and remodeled during the first 2 years of life
throughout childhood, circuits are initiated, remodeled and stabilized as skills are learned and mastered
What are the rates of synaptogenesis and synaptic pruning in adults?
it is slow
What domains do chronic disorders affecting the central nervous system function during the developmental period?
motor skills
cognition
communication
behavior
What are some examples of neurodevelopmental disorders?
developmental delay and regression
intellectual disability
cerebral palsy
epilepsy
autism spectrum disorder
specific learning disabilities
language disorder
attention deficit/hyperactivity disorder
deafness
blindness
What are etiological factors causing neurodevelopmental disorders?
hypoxic-ischemic injury (during delivery brain lacks oxygen causes damage)
trauma
toxic exposure (could happen during pregnancy)
infections
immunologic factors
nutritional factors (not sufficient protein)
aging/maturation
iatrogenic disorders
oncologic disorders
genetic diseases (metabolic genetic, neurogenetic, structural brain malformations)
What are some examples of developmental domains?
gross motor
fine motor
speech/language
cognition
social/personal
activities of daily living
What is global developmental delay?
GDD is subset of developmental disabilities
> 2 SDs below age-matched peers in two or more aspects of developmental domains
heterogeneous etiology
estimated prevalence of GDD 1-3% in children <5 years of age
4 million newborns/year in US & Canada; 40,000-120,000 will manifest with GDD
When to suspect genetic diseases & consider a referral to a genetic clinic when viewing the medical history of a patient?
earlier age of onset of disease than expected
FTT/protein aversion
recurrent somnolence & coma
behavioral problems
seizures
hypotonia
loss of skills
ataxia/coordination problems
hair abnormalities
deafness
no other known or identified risk factors
When to suspect genetic diseases & consider a referral to a genetic clinic when viewing the family history of a patient?
ID/GDD
psychiatric disorders
congenital malformations
miscarriage/stillbirths/SIDS
early childhood deaths
maternal health
maternal side migraine/diabetes
parental consanguinity
ethnic predisposition to certain genetic diseases
other affected family members, suggesting Mendelian inheritance pattern
What are the implications of etiologic determination?
access to research treatment protocols
prognosis
ongoing medical management
assessment of recurrence risk
implementation of prevention programs
limiting further unnecessary testing
surveillance for known complications
What is inheritance?
genetic information is passed on from parent to child
What is the Human Genome Project (HGP)?
international research initiative between 1990-2003
the sequencing of the human genome involved researchers from 20 separate universities and research centers across the US, UK, France, Germany, Japan, and China
generated the first sequence of the human genome
studied several organisms e.g. E. coli, baker’s yeast, fruit fly, nematode and mouse
one of the most ambitious and important scientific endeavors in human history
produced a genome sequence that accounted for 92% of the human genome
about 20,500 genes in each human (the complete set of human genes)
location of all genes known in human genome
What is genotype?
individual’s actual DNA sequence at a specific locus (location on a chromosome)
What is phenotype?
observable ways in which that DNA sequence manifests in the individual, such as eye color, hair color, or susceptibility to a disease
What does allele mean?
an alternate form of a gene