Clinical Genetics

Support Material

Hospital Geral de Santo

2007-2008 António
Concepts

Gene - basic unit of heredity, consisting of a segment of DNA arranged

in a linear manner along a chromosome.
Genome - The complete DNA sequence, containing all genetic
information and supporting proteins, in the chromosomes of an
individual or species
Chromosome - Physical structure consisting of a large DNA molecule
organized into genes and supported by proteins called chromatin
Allele - One version of a gene at a given location (locus) along a
chromosome

genotype: The genetic constitution of an organism or cell; also refers to

the specific set of alleles inherited at a locus
phenotype: The observable physical and/or biochemical characteristics
of the expression of a gene; the clinical presentation of an individual
with a particular genotype
haplotype: set of closely linked segments of DNA assumed to be
inherited in block; used in linkage analysis or when a given trait is in
linkage disequilibrium with a marker or set of markers

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The Code

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The Code

From Livingstone, C. D. and Barton, G. J. (1993),

"Protein Sequence Alignments: A Strategy for the Hierarchical Analysis of Residue Conservation", Comp. Appl. Bio. Sci., 9, 745-756.

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Concepts

Mutation/Sequence alteration - Any alteration in a gene

from its natural state; may be disease-causing or a benign,
normal variant
Polymorphism: Natural variations in a gene, DNA sequence,
protein, or chromosome that have no adverse effect on the
individual and occur with fairly high frequency in the general

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Concepts

Point Mutations
Substitutions
Missense – AA substitutions
...CTG UGU... Cysteine
‘Silent’
...CTG UGC... Cysteine
...CTG UGG... Tryptophan
Nonsense – premature Stop codon
...CTG UGC... Cysteine
...CTG UGA... STOP

RNA Processing – destroy Splice, cap, polyadenylation

sites or create cryptic

Regulatory – transcription factor binding

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Concepts

Ins/del
Insertion
...CTG UGC...
...CTG UGCTGG...
Deletion
...CTG 
UGC...
...CTG U...
In-frame/out-frame - (not) leads to a shift in the reading frame

...The fat cat sat...

... fat cat sat ... In-frame

 fat cat sat...

...The
... Hef atc ats at... Frameshift (out of frame)

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Modes of Inheritance

Autosomal Dominant

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Modes of Inheritance

Autosomal Recessive

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Modes of Inheritance

X-Linked (recessive/dominant)

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Modes of Inheritance

Mitochondrial

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Modes of Inheritance

Imprinting

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Pedigree

Symbols

Rules
Landscape
Proband/consultant
Sibship order
Generation zones
Lines
Medical Termination
of Pregnancy 12Wk
anecephaly