Genetics and Family History

Behm, Kelly Mullholand

doi:10.1007/978-3-319-99817-6_7

Kelly Mullholand Behm⁵

2097 Accesses

Abstract

This chapter describes principles of genetics and family history that are relevant to the practice of clinical endocrinology. It begins with a review of historical eras that provides context for how two seemingly distinct specialties have become intricately interwoven. Genetics concepts are then explained in a progression from basic to complex, each section building on the previous, with clinical examples included to help readers develop a comprehensive understanding without becoming overwhelmed. Topics covered include DNA and RNA structure and function, the genetic code, transcription, translation, exons, introns, gene expression, gene locus, alleles, genotype, phenotype, Mendelian and non-Mendelian patterns of inheritance, epigenetics, gene mutations, chromosomal structural and copy number abnormalities, and cytogenetic and molecular genetic testing methodologies and interpretation.

The Mendelian inheritance section outlines the three laws of Mendelian inheritance and associated inheritance patterns including homozygous and heterozygous, autosomal and pseudoautosomal, dominant and recessive. Non-Mendelian patterns of inheritance described include co-dominance, linkage, sex-linked, multiple alleles, complex polygenic or multifactorial, and mitochondrial.

Gene mutations discussed include point, missense, nonsense, insertion, deletion, duplication, frameshift, substitution, and repeat expansions. Chromosomal abnormalities described include translocations, deletions, duplications, inversions, isochromosomes, dicentric, ring, and aneuploidies resulting from meiotic and mitotic nondisjunction.

The genetic testing section covers karyotyping, fluorescent in situ hybridization, microarrays, gene expression analysis, direct sequencing analysis, and methylation analysis. The section on family history provides information about publicly available tools for collecting genetic and endocrine history data, as well as a detailed description of how to create and use pedigrees to aid in clinical decision-making and communication with patients and their families.

The chapter concludes with a practical discussion of nursing implications, a recommended reading section, and an extensive list of supplemental educational materials and resources. Supplemental materials include a genetics glossary, a list of online resources for information on genetics concepts introduced within the chapter, a list of genetics-based peer-reviewed journals, a list of professional organizations and societies for nurses interested in genetics, and a list of current textbooks on genetics.

The recommended reading section contains a list of online and print publications providing additional in-depth information on genetics in human endocrinology, nursing competencies in genetics, using analogies in patient education, legal and ethical implications of genetics in the clinical setting, issues surrounding disclosure of genetic diagnoses, clinical case studies, interactive pedigree software, epigenetics, molecular genetics testing, gene therapy, additional internet genetics resources, and the future of genetics in endocrinology.

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Notes

1.
Key terms definitions were derived from National Human Genome Research Institute (2014).

Abbreviations

2n:: Diploid
3′:: 3-prime
3-M:: Syndrome causing short stature, unusual facial features, and skeletal abnormalities first identified by researchers named Miller, McKusick, and Malvaux
5′:: 5-prime
A:: Adenine
aCGH:: Array comparative genomic hybridization
ACTH:: Adrenocorticotropic hormone
AR:: Androgen receptor
arr:: Array
bp:: Base pairs
BWS:: Beckwith–Wiedemann syndrome
C:: Cytosine
CAG:: Cytosine-adenine-guanine nucleotide sequence
CDKN1B:: Cyclin dependent kinase inhibitor 1B
cDNA:: Complementary DNA
CGH:: Comparative genomic hybridization
CH₃:: Methyl group
CH₃CO:: Acetyl group
CNV:: Copy number variants or copy number variations
CpG:: Cytosine-phosphate-guanine (cytosine and guanine separated by a phosphate)
CYP212A :: Cytochrome P450 family 21 subfamily A member 2
del or dn:: Deletion
der:: Derivative chromosome
dp:: Duplication
DNA:: Deoxyribonucleic acid
FGD:: Familial glucocorticoid deficiency
FGFR3 :: Fibroblast growth factor receptor 3
FISH:: Fluorescent in situ hybridization
FMR1 :: Fragile X mental retardation 1
G:: Guanine
GEM:: Gene expression microarray
GH:: Growth hormone
GNAS :: Guanine nucleotide-binding protein alpha subunit or g-protein alpha subunit
HDSNP-array:: High-density single nucleotide polymorphism array
i:: Isochromosome
ins:: Insertion
inv:: Inversion
kb:: Kilobase pairs
mat:: Maternally derived chromosome
Mb:: Megabase pairs
MEN1 :: Multiple endocrine neoplasia type 1 or menin 1
MEN4:: Multiple endocrine neoplasia type 4
MIDD:: Maternally inherited diabetes and deafness or mitochondrial diabetes and deafness
miRNA:: MicroRNAs
MODY5:: Maturity-onset diabetes of the young type 5
mRNA:: Messenger RNA
mtDNA:: Mitochondrial DNA
n:: Haploid
NGS:: Next-generation sequencing
p:: Short arm of a chromosome
PCOS:: Polycystic ovarian syndrome
PCR:: Polymerase chain reaction
PHEX :: Phosphate regulating endopeptidase homolog X-linked
PTPN11 :: Protein tyrosine phosphatase, non-receptor type 11
q:: Long arm of a chromosome
RCAD:: Renal cysts and diabetes syndrome
RNA:: Ribonucleic acid
rRNA:: Ribosomal RNA
SHOX :: Short stature homeobox
SNP:: Single nucleotide polymorphism
SNP-array:: Single nucleotide polymorphism array
SOS1 :: Son of sevenless homolog 1 or SOS Ras/Rac guanine nucleotide exchange factor 1
SOX3 :: SRY-box 3 or SRY-related HMG-box 3 (Sex-determining region Y-related high-mobility-group box transcription factor 3)
SRY :: Sex-determining region Y
T:: Thymine
t:: Translocation
tRNA:: Transfer RNA
TSH:: Thyroid stimulating hormone
U:: Uracil
VHL :: Von Hippel-Lindau
WES:: Whole-exome sequencing
WGS:: Whole-genome sequencing
wt:: Wild type allele
Xce :: X chromosome controlling element
Xic:: X-inactivation center
Xist :: X inactive specific transcript

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Orlando, FL, USA
Kelly Mullholand Behm

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School of Health Sciences, City, University of London, London, UK
Sofia Llahana
Department of Oncology, Skåne University Hospital, Lund, Sweden
Cecilia Follin
Northwest Pituitary Center Oregon Health and Sciences University, Portland, OR, USA
Christine Yedinak
Churchill Hospital, University of Oxford, Oxford, UK
Ashley Grossman

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Behm, K.M. (2019). Genetics and Family History. In: Llahana, S., Follin, C., Yedinak, C., Grossman, A. (eds) Advanced Practice in Endocrinology Nursing. Springer, Cham. https://doi.org/10.1007/978-3-319-99817-6_7

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DOI: https://doi.org/10.1007/978-3-319-99817-6_7
Published: 27 February 2019
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