18 Genetics and Development 2 Flashcards
List and describe the processes involved in morphogenesis 4
- Proliferation = cell division
- Differentiation = acquisition by a cell of novel characteristics specific to cell type or tissue
- Migration = cell movement within the embryo
- Apoptosis = programmed cell death
Describe how developmental genes control development
Transcription factors control development
- Different combinations of transcription factors expressed at different places and at different times -> **Spatiotemporal regulation of development **
Describe how chromosomal abnormalities arise: (5)
- Abnormal chromosome segregation
- Recurrent chromosomal syndromes
- Idiopathic chromosome abnormalities
- Unbalanced familial abnormalities
- Syndromes involving genomic imprinting
Underlying mechanism of the five chromosomal abnormalities:
- Abnormal chromosome segregation - nondisjunction
- Recurrent chromosomal syndromes - Recombination at segmental duplications
- Idiopathic chromosome abnormalities - sporadic, variable breakpoints // De novo balanced translocations
- Unbalanced familial abnormalities: Unbalanced segregation
- Syndromes involving genomic imprinting: Any event that reveals imprinted gene(s)
Define teratogen
Any agent that can disturb the development of an embryo or fetus
What are the (4) factors that influence teratogenicity
- Timing
- Dosage
- Genotype of Fetus
- Genotype of mother
Describe the (4) factors that influence teratogenicity:
1. Timing
2. Dosage
3. Genotype of Fetus
4. Maternal Genotype
- Timing: Gestational age at time of exposure to teratogen (dif organs develop at dif times so sensitivy to teratogen and affected organ(s) will vary)
- Dosage - How much of the teratogen was the fetus exposed
- Genotype of Fetus - may be more or less resistant to teratogen because of inactivation of teratogen
- Genotype of mother - differ in ability to detoxify the teratogen
What is a morphogen?
- substance produced by cells in particular region of embryo
- diffuses from its point of origin through the tissues of the embryo
- Form a concentration gradient
- Cells undergo specification and then determination to different fates
What is SHH and what is its role in development?
SHH - sonic hedgehog
- morphogen that generates a gradient
- Induces and organizes the different cell types and tissues in the developing brain and spinal cord
Abnormalities in SHH can lead to:
- holoprosencephaly = failure of the midface and forebrain to develop
- cleft lip and palate
- hypotelorism (eyes close together)
- Variable expressivitiy within the same family
- Affected by other modifier genes, chance, env’t, or combination of those three
What is FGF? Examples of abnormalities?
- Fibroblast growth factors
- one of many ligand-receptor pairs important in development
- Involved in bone development
- eg: achodroplasia; FGFR3 mutations
Consequences/Examples of Abnormal Chromosome Segregation
Abnormal Chromosome Segregation
Aneuploidy
- Down syndrome
- Klinefelter syndrome
- Uniparental disomy
Underlying mechanism: Nondisjunction
Consequences/Examples of Recurrent chromosomal syndromes
- Duplication/deletion syndromes
- Copy number variation
Underlying mechanism: Recombination at segmental duplications
Consequences/Examples of idiopathic chromosome abnormalities:
Deletion syndromes:
- Cri du chat syndrome (del5p15)
- 1p36 deletion syndrome
Consequences/Examples of unbalanced familial abnormalities
Offspring of balanced translocations
Offspring of pericentric inversions
Consequences/Examples of Syndromes involving genomic imprinting?
- Prader-willi
- Angelman syndromes
Underlying mechanism = any event that reveals imprinted gene(s)
Humans inherit two alleles from mother and father, both are functional for the majority of the genes, but sometimes one is turned off or “stamped” and doesn’t show in offspring, that gene is imprinted. Imprinting means that that gene is silenced, and gene from other parent is expressed
What is gene imprinting? Consequences of improper imprinting?
- Humans inherit two alleles from mother and father, both are functional for the majority of the genes, but sometimes one is turned off or “stamped” and doesn’t show in offspring, that gene is imprinted. Imprinting means that that gene is silenced, and gene from other parent is expressed
- An individual normally has one active copy of an imprinted gene.
- Improper imprinting can result in an individual having two active copies or two inactive copies. This can lead to severe developmental abnormalities, cancer, and other problems
What is the most common chromosomal abnormality
Aneuploidy
- error in chromosome segregationg
What is meiotic nondisjunction?
- Failure of a pair of chromosomes to disjoin properly
- poorly understood in humans
Monosomy vs Trisomy?
- Trisomy disorders occur when you have an extra copy of a chromosome.
- Monosomy occurs when you are missing a copy of a chromosome.
- Both of these genetic conditions are the result of a genetic mutation where your cells don’t divide as they should
- Monosomies are more deleterious than trisomies and are generally non-viable (unless monosomy X)
- Complete trisomies are viable for chromosomes: 13, 18, 21, X and Y
Complete trisomies are viable for chromosomes: (5)
Complete trisomies are viable for chromosomes: 13, 18, 21, X and Y
Describe embyopathy/FAS
- Alcohol = teratogen = cause of FAS
- Leading cause of mental retaration arising from the action of known teratogens
- Group of physical and mental birth defects that are the direct result of drinking EtOH during pregnancy
- Substantial public health problem and societal economic burden
- 100% preventable
FAS = Fetal alcohol syndrome
