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Genetics and Family History

  • Kelly Mullholand Behm
Chapter

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.

Keywords

Genetics DNA Expression Inheritance Mutation Testing Pedigree 

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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© Springer Nature Switzerland AG 2019

Authors and Affiliations

  • Kelly Mullholand Behm
    • 1
  1. 1.OrlandoUSA

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